Skip to main content
SpringerLink
Log in

Innate Immunity to Malaria

  • Chapter
  • First Online:
Malaria

Chapter Summary

The innate immune response to malaria has always attracted the interest of researchers trying to understand the basis for the high fevers observed in malaria patients during blood-stage infection and the lack of an apparent response to the liver-stage infection. Research targeting specific parts of the immune response has contributed to a basic understanding of the concepts that play a role in malaria-induced inflammation. Given the complexity of the immune response in general and to the parasite in particular, some findings have been contradictory. Here we summarize a large body of work including the host innate immune response to a Plasmodium liver and blood-stage infection, focusing on the different parasite- and host-derived molecules that trigger inflammation, the immune cell types involved, and the role of different cytokines in inflammation and pathology of malaria.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

DCs:

Dendritic cells

GPI:

Glycosylphosphatidylinositol

IFN:

Interferon

Ifnar:

Interferon alpha receptor

ISG:

Interferon-stimulated gene

MAVS:

Mitochondrial antiviral-signaling protein

MDA5:

Melanoma differentiation-associated protein 5

NK:

Natural killer cells

NKT:

Natural killer T cells

PBMC:

Peripheral blood mononuclear cells

ROS:

Reactive oxygen species

TLR:

Toll-like receptors

References

  1. Prudencio M, Rodriguez A, Mota MM (2006) The silent path to thousands of merozoites: the Plasmodium liver stage. Nat Rev Microbiol 4(11):849–856. doi:10.1038/nrmicro1529

    Article  CAS  PubMed  Google Scholar 

  2. Sturm A, Amino R, van de Sand C, Regen T, Retzlaff S, Rennenberg A, Krueger A, Pollok JM, Menard R, Heussler VT (2006) Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science 313(5791):1287–1290. doi:10.1126/science.1129720

    Article  CAS  PubMed  Google Scholar 

  3. Mackintosh CL, Beeson JG, Marsh K (2004) Clinical features and pathogenesis of severe malaria. Trends Parasitol 20(12):597–603

    Article  CAS  PubMed  Google Scholar 

  4. Kwiatkowski D (1995) Malarial toxins and the regulation of parasite density. Parasitol Today 11(6):206–212

    Article  CAS  PubMed  Google Scholar 

  5. Hemmer CJ, Holst FG, Kern P, Chiwakata CB, Dietrich M, Reisinger EC (2006) Stronger host response per parasitized erythrocyte in Plasmodium vivax or ovale than in Plasmodium falciparum malaria. Trop Med Int Health 11(6):817–823. doi:10.1111/j.1365-3156.2006.01635.x

    Article  PubMed  Google Scholar 

  6. Yeo TW, Lampah DA, Tjitra E, Piera K, Gitawati R, Kenangalem E, Price RN, Anstey NM (2010) Greater endothelial activation, Weibel-Palade body release and host inflammatory response to Plasmodium vivax, compared with Plasmodium falciparum: a prospective study in Papua, Indonesia. J Infect Dis 202(1):109–112. doi:10.1086/653211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Goncalves RM, Scopel KK, Bastos MS, Ferreira MU (2012) Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum? PLoS One 7(9), e44394. doi:10.1371/journal.pone.0044394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Branch O, Casapia WM, Gamboa DV, Hernandez JN, Alava FF, Roncal N, Alvarez E, Perez EJ, Gotuzzo E (2005) Clustered local transmission and asymptomatic Plasmodium falciparum and Plasmodium vivax malaria infections in a recently emerged, hypoendemic Peruvian Amazon community. Malar J 4:27

    Article  PubMed  PubMed Central  Google Scholar 

  9. Epiphanio S, Mikolajczak SA, Goncalves LA, Pamplona A, Portugal S, Albuquerque S, Goldberg M, Rebelo S, Anderson DG, Akinc A, Vornlocher HP, Kappe SH, Soares MP, Mota MM (2008) Heme oxygenase-1 is an anti-inflammatory host factor that promotes murine Plasmodium liver infection. Cell Host Microbe 3(5):331–338. doi:10.1016/j.chom.2008.04.003

    Article  CAS  PubMed  Google Scholar 

  10. Khan ZM, Ng C, Vanderberg JP (1992) Early hepatic stages of Plasmodium berghei: release of circumsporozoite protein and host cellular inflammatory response. Infect Immun 60(1):264–270

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Leiriao P, Mota MM, Rodriguez A (2005) Apoptotic Plasmodium-infected hepatocytes provide antigens to liver dendritic cells. J Infect Dis 191(10):1576–1581. doi:10.1086/429635

    Article  PubMed  Google Scholar 

  12. van de Sand C, Horstmann S, Schmidt A, Sturm A, Bolte S, Krueger A, Lutgehetmann M, Pollok JM, Libert C, Heussler VT (2005) The liver stage of Plasmodium berghei inhibits host cell apoptosis. Mol Microbiol 58(3):731–742. doi:10.1111/j.1365-2958.2005.04888.x

    Article  PubMed  CAS  Google Scholar 

  13. Golgi C (1893) Sulle febbri malariche estivo-autunnali di Roma. Gazzetta Medica di Pavia 2:2:481–493; 505–520; 553–559

    Google Scholar 

  14. Schofield L, Hackett F (1993) Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. J Exp Med 177(1):145–153

    Article  CAS  PubMed  Google Scholar 

  15. Bautista JM, Marin-Garcia P, Diez A, Azcarate IG, Puyet A (2014) Malaria proteomics: insights into the parasite-host interactions in the pathogenic space. J Proteome 97:107–125. doi:10.1016/j.jprot.2013.10.011

    Article  CAS  Google Scholar 

  16. Krishnegowda G, Hajjar AM, Zhu J, Douglass EJ, Uematsu S, Akira S, Woods AS, Gowda DC (2005) Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: cell signaling receptors, glycosylphosphatidylinositol (GPI) structural requirement, and regulation of GPI activity. J Biol Chem 280(9):8606–8616. doi:10.1074/jbc.M413541200

    Article  CAS  PubMed  Google Scholar 

  17. Debierre-Grockiego F, Schofield L, Azzouz N, Schmidt J, Santos de Macedo C, Ferguson MA, Schwarz RT (2006) Fatty acids from Plasmodium falciparum down-regulate the toxic activity of malaria glycosylphosphatidylinositols. Infect Immun 74(10):5487–5496. doi:10.1128/IAI.01934-05

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wu X, Gowda NM, Kumar S, Gowda DC (2010) Protein-DNA complex is the exclusive malaria parasite component that activates dendritic cells and triggers innate immune responses. J Immunol 184(8):4338–4348. doi:10.4049/jimmunol.0903824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mockenhaupt FP, Cramer JP, Hamann L, Stegemann MS, Eckert J, Oh NR, Otchwemah RN, Dietz E, Ehrhardt S, Schroder NW, Bienzle U, Schumann RR (2006) Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci U S A 103(1):177–182. doi:10.1073/pnas.0506803102

    Article  CAS  PubMed  Google Scholar 

  20. Panigrahi S, Kar A, Tripathy S, Mohapatra MK, Dhangadamajhi G (2016) Genetic predisposition of variants in TLR2 and its co-receptors to severe malaria in Odisha, India. Immunol Res 64(1):291–302. doi:10.1007/s12026-015-8749-7

    Article  CAS  PubMed  Google Scholar 

  21. Manning L, Cutts J, Stanisic DI, Laman M, Carmagnac A, Allen S, O’Donnell A, Karunajeewa H, Rosanas-Urgell A, Siba P, Davis TM, Michon P, Schofield L, Rockett K, Kwiatkowski D, Mueller I (2016) A Toll-like receptor-1 variant and its characteristic cellular phenotype is associated with severe malaria in Papua New Guinean children. Genes Immun 17(1):52–59. doi:10.1038/gene.2015.50

    Article  CAS  PubMed  Google Scholar 

  22. Franklin BS, Mangan MS, Latz E (2016) Crystal formation in inflammation. Annu Rev Immunol 34:173–202. doi:10.1146/annurev-immunol-041015-055539

    Article  PubMed  CAS  Google Scholar 

  23. Coban C, Ishii KJ, Kawai T, Hemmi H, Sato S, Uematsu S, Yamamoto M, Takeuchi O, Itagaki S, Kumar N, Horii T, Akira S (2005) Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J Exp Med 201(1):19–25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Coban C, Igari Y, Yagi M, Reimer T, Koyama S, Aoshi T, Ohata K, Tsukui T, Takeshita F, Sakurai K, Ikegami T, Nakagawa A, Horii T, Nunez G, Ishii KJ, Akira S (2010) Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9. Cell Host Microbe 7(1):50–61

    Article  CAS  PubMed  Google Scholar 

  25. Jaramillo M, Gowda DC, Radzioch D, Olivier M (2003) Hemozoin increases IFN-gamma-inducible macrophage nitric oxide generation through extracellular signal-regulated kinase- and NF-kappa B-dependent pathways. J Immunol 171(8):4243–4253

    Article  CAS  PubMed  Google Scholar 

  26. Shio MT, Eisenbarth SC, Savaria M, Vinet AF, Bellemare MJ, Harder KW, Sutterwala FS, Bohle DS, Descoteaux A, Flavell RA, Olivier M (2009) Malarial hemozoin activates the NLRP3 inflammasome through Lyn and Syk kinases. PLoS Pathog 5(8), e1000559. doi:10.1371/journal.ppat.1000559

    Article  PubMed  CAS  Google Scholar 

  27. Dostert C, Guarda G, Romero JF, Menu P, Gross O, Tardivel A, Suva ML, Stehle JC, Kopf M, Stamenkovic I, Corradin G, Tschopp J (2009) Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS One 4(8), e6510. doi:10.1371/journal.pone.0006510

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Parroche P, Lauw FN, Goutagny N, Latz E, Monks BG, Visintin A, Halmen KA, Lamphier M, Olivier M, Bartholomeu DC, Gazzinelli RT, Golenbock DT (2007) Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9. Proc Natl Acad Sci U S A 104(6):1919–1924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Barrera V, Skorokhod OA, Baci D, Gremo G, Arese P, Schwarzer E (2011) Host fibrinogen stably bound to hemozoin rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin: a new paradigm of hemozoin action. Blood 117(21):5674–5682. doi:10.1182/blood-2010-10-312413

    Article  CAS  PubMed  Google Scholar 

  30. Pichyangkul S, Saengkrai P, Webster HK (1994) Plasmodium falciparum pigment induces monocytes to release high levels of tumor necrosis factor-alpha and interleukin-1 beta. Am J Trop Med Hyg 51(4):430–435

    CAS  PubMed  Google Scholar 

  31. Kalantari P, DeOliveira RB, Chan J, Corbett Y, Rathinam V, Stutz A, Latz E, Gazzinelli RT, Golenbock DT, Fitzgerald KA (2014) Dual engagement of the NLRP3 and AIM2 inflammasomes by Plasmodium-derived hemozoin and DNA during malaria. Cell Rep 6(1):196–210. doi:10.1016/j.celrep.2013.12.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Tyberghein A, Deroost K, Schwarzer E, Arese P, Van den Steen PE (2014) Immunopathological effects of malaria pigment or hemozoin and other crystals. Biofactors 40(1):59–78. doi:10.1002/biof.1119

    Article  CAS  PubMed  Google Scholar 

  33. Onishi M, Kitano M, Taniguchi K, Homma T, Kobayashi M, Sato A, Coban C, Ishii KJ (2014) Hemozoin is a potent adjuvant for hemagglutinin split vaccine without pyrogenicity in ferrets. Vaccine 32(25):3004–3009. doi:10.1016/j.vaccine.2014.03.072

    Article  CAS  PubMed  Google Scholar 

  34. Uraki R, Das SC, Hatta M, Kiso M, Iwatsuki-Horimoto K, Ozawa M, Coban C, Ishii KJ, Kawaoka Y (2014) Hemozoin as a novel adjuvant for inactivated whole virion influenza vaccine. Vaccine 32(41):5295–5300. doi:10.1016/j.vaccine.2014.07.079

    Article  CAS  PubMed  Google Scholar 

  35. Gowda NM, Wu X, Gowda DC (2011) The nucleosome (histone-DNA complex) is the TLR9-specific immunostimulatory component of Plasmodium falciparum that activates DCs. PLoS One 6(6), e20398. doi:10.1371/journal.pone.0020398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hirako IC, Gallego-Marin C, Ataide MA, Andrade WA, Gravina H, Rocha BC, de Oliveira RB, Pereira DB, Vinetz J, Diamond B, Ram S, Golenbock DT, Gazzinelli RT (2015) DNA-containing immunocomplexes promote inflammasome assembly and release of pyrogenic cytokines by CD14+ CD16+ CD64high CD32low Inflammatory Monocytes from Malaria Patients. MBio 6(6):e01605–e01615. doi:10.1128/mBio.01605-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sharma S, DeOliveira RB, Kalantari P, Parroche P, Goutagny N, Jiang Z, Chan J, Bartholomeu DC, Lauw F, Hall JP, Barber GN, Gazzinelli RT, Fitzgerald KA, Golenbock DT (2011) Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome. Immunity 35(2):194–207. doi:10.1016/j.immuni.2011.05.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lepenies B, Cramer JP, Burchard GD, Wagner H, Kirschning CJ, Jacobs T (2008) Induction of experimental cerebral malaria is independent of TLR2/4/9. Med Microbiol Immunol 197(1):39–44. doi:10.1007/s00430-007-0057-y

    Article  PubMed  Google Scholar 

  39. Baccarella A, Fontana MF, Chen EC, Kim CC (2013) Toll-like receptor 7 mediates early innate immune responses to malaria. Infect Immun 81(12):4431–4442. doi:10.1128/IAI.00923-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Esposito S, Molteni CG, Zampiero A, Baggi E, Lavizzari A, Semino M, Daleno C, Groppo M, Scala A, Terranova L, Miozzo M, Pelucchi C, Principi N (2012) Role of polymorphisms of toll-like receptor (TLR) 4, TLR9, toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A genes in malaria susceptibility and severity in Burundian children. Malar J 11:196. doi:10.1186/1475-2875-11-196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Munde EO, Okeyo WA, Anyona SB, Raballah E, Konah S, Okumu W, Ogonda L, Vulule J, Ouma C (2012) Polymorphisms in the Fc gamma receptor IIIA and Toll-like receptor 9 are associated with protection against severe malarial anemia and changes in circulating gamma interferon levels. Infect Immun 80(12):4435–4443. doi:10.1128/IAI.00945-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Campino S, Forton J, Auburn S, Fry A, Diakite M, Richardson A, Hull J, Jallow M, Sisay-Joof F, Pinder M, Molyneux ME, Taylor TE, Rockett K, Clark TG, Kwiatkowski DP (2009) TLR9 polymorphisms in African populations: no association with severe malaria, but evidence of cis-variants acting on gene expression. Malar J 8:44. doi:10.1186/1475-2875-8-44

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Liehl P, Zuzarte-Luis V, Chan J, Zillinger T, Baptista F, Carapau D, Konert M, Hanson KK, Carret C, Lassnig C, Muller M, Kalinke U, Saeed M, Chora AF, Golenbock DT, Strobl B, Prudencio M, Coelho LP, Kappe SH, Superti-Furga G, Pichlmair A, Vigario AM, Rice CM, Fitzgerald KA, Barchet W, Mota MM (2014) Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection. Nat Med 20(1):47–53. doi:10.1038/nm.3424

    Article  CAS  PubMed  Google Scholar 

  44. Orengo JM, Evans JE, Bettiol E, Leliwa-Sytek A, Day K, Rodriguez A (2008) Plasmodium-induced inflammation by uric acid. PLoS Pathog 4(3), e1000013

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Orengo JM, Leliwa-Sytek A, Evans JE, Evans B, van de Hoef D, Nyako M, Day K, Rodriguez A (2009) Uric acid is a mediator of the Plasmodium falciparum-induced inflammatory response. PLoS One 4(4), e5194

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. van de Hoef DL, Coppens I, Holowka T, Ben Mamoun C, Branch O, Rodriguez A (2013) Plasmodium falciparum-derived uric acid precipitates induce maturation of dendritic cells. PLoS One 8(2), e55584. doi:10.1371/journal.pone.0055584

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440(7081):237–241

    Article  CAS  PubMed  Google Scholar 

  48. Ataide MA, Andrade WA, Zamboni DS, Wang D, Souza Mdo C, Franklin BS, Elian S, Martins FS, Pereira D, Reed G, Fitzgerald KA, Golenbock DT, Gazzinelli RT (2014) Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection. PLoS Pathog 10(1), e1003885. doi:10.1371/journal.ppat.1003885

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Guermonprez P, Helft J, Claser C, Deroubaix S, Karanje H, Gazumyan A, Darasse-Jeze G, Telerman SB, Breton G, Schreiber HA, Frias-Staheli N, Billerbeck E, Dorner M, Rice CM, Ploss A, Klein F, Swiecki M, Colonna M, Kamphorst AO, Meredith M, Niec R, Takacs C, Mikhail F, Hari A, Bosque D, Eisenreich T, Merad M, Shi Y, Ginhoux F, Renia L, Urban BC, Nussenzweig MC (2013) Inflammatory Flt3l is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection. Nat Med 19(6):730–738. doi:10.1038/nm.3197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sarma PS, Mandal AK, Khamis HJ (1998) Allopurinol as an additive to quinine in the treatment of acute complicated falciparum malaria. Am J Trop Med Hyg 58(4):454–457

    CAS  PubMed  Google Scholar 

  51. Ismail N, Wang Y, Dakhlallah D, Moldovan L, Agarwal K, Batte K, Shah P, Wisler J, Eubank TD, Tridandapani S, Paulaitis ME, Piper MG, Marsh CB (2013) Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood 121(6):984–995. doi:10.1182/blood-2011-08-374793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Nantakomol D, Dondorp AM, Krudsood S, Udomsangpetch R, Pattanapanyasat K, Combes V, Grau GE, White NJ, Viriyavejakul P, Day NP, Chotivanich K (2011) Circulating red cell-derived microparticles in human malaria. J Infect Dis 203(5):700–706. doi:10.1093/infdis/jiq104

    Article  PubMed  PubMed Central  Google Scholar 

  53. Couper KN, Barnes T, Hafalla JC, Combes V, Ryffel B, Secher T, Grau GE, Riley EM, de Souza JB (2010) Parasite-derived plasma microparticles contribute significantly to malaria infection-induced inflammation through potent macrophage stimulation. PLoS Pathog 6(1), e1000744. doi:10.1371/journal.ppat.1000744

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Mantel PY, Hoang AN, Goldowitz I, Potashnikova D, Hamza B, Vorobjev I, Ghiran I, Toner M, Irimia D, Ivanov AR, Barteneva N, Marti M (2013) Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system. Cell Host Microbe 13(5):521–534. doi:10.1016/j.chom.2013.04.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Wheway J, Latham SL, Combes V, Grau GE (2014) Endothelial microparticles interact with and support the proliferation of T cells. J Immunol 193(7):3378–3387. doi:10.4049/jimmunol.1303431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Campos FM, Franklin BS, Teixeira-Carvalho A, Filho AL, de Paula SC, Fontes CJ, Brito CF, Carvalho LH (2010) Augmented plasma microparticles during acute Plasmodium vivax infection. Malar J 9:327. doi:10.1186/1475-2875-9-327

    Article  PubMed  PubMed Central  Google Scholar 

  57. Combes V, Taylor TE, Juhan-Vague I, Mege JL, Mwenechanya J, Tembo M, Grau GE, Molyneux ME (2004) Circulating endothelial microparticles in malawian children with severe falciparum malaria complicated with coma. JAMA 291(21):2542–2544. doi:10.1001/jama.291.21.2542-b

    CAS  PubMed  Google Scholar 

  58. Sahu U, Sahoo PK, Kar SK, Mohapatra BN, Ranjit M (2013) Association of TNF level with production of circulating cellular microparticles during clinical manifestation of human cerebral malaria. Hum Immunol 74(6):713–721. doi:10.1016/j.humimm.2013.02.006

    Article  CAS  PubMed  Google Scholar 

  59. McGinn CM, MacDonnell BF, Shan CX, Wallace R, Cummins PM, Murphy RP (2016) Microparticles: a pivotal nexus in vascular homeostasis and disease. Curr Clin Pharmacol 11(1):28–42

    Article  CAS  PubMed  Google Scholar 

  60. Francis SE, Sullivan DJ Jr, Goldberg DE (1997) Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu Rev Microbiol 51:97–123. doi:10.1146/annurev.micro.51.1.97

    Article  CAS  PubMed  Google Scholar 

  61. Liu M, Amodu AS, Pitts S, Patrickson J, Hibbert JM, Battle M, Ofori-Acquah SF, Stiles JK (2012) Heme mediated STAT3 activation in severe malaria. PLoS One 7(3), e34280. doi:10.1371/journal.pone.0034280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Liu M, Wilson NO, Hibbert JM, Stiles JK (2013) STAT3 regulates MMP3 in heme-induced endothelial cell apoptosis. PLoS One 8(8), e71366. doi:10.1371/journal.pone.0071366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Liu M, Dickinson-Copeland C, Hassana S, Stiles JK (2016) Plasmodium-infected erythrocytes (pRBC) induce endothelial cell apoptosis via a heme-mediated signaling pathway. Drug Des Devel Ther 10:1009–1018. doi:10.2147/DDDT.S96863

    Article  PubMed  PubMed Central  Google Scholar 

  64. Dickinson-Copeland CM, Wilson NO, Liu M, Driss A, Salifu H, Adjei AA, Wilson M, Gyan B, Oduro D, Badu K, Botchway F, Anderson W, Bond V, Bacanamwo M, Singh S, Stiles JK (2015) Heme-mediated induction of CXCL10 and depletion of CD34+ progenitor cells is toll-like receptor 4 dependent. PLoS One 10(11), e0142328. doi:10.1371/journal.pone.0142328

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Metzger A, Mukasa G, Shankar AH, Ndeezi G, Melikian G, Semba RD (2001) Antioxidant status and acute malaria in children in Kampala, Uganda. Am J Trop Med Hyg 65:115–119

    CAS  PubMed  Google Scholar 

  66. Narsaria N, Mohanty C, Das BK, Mishra SP, Prasad R (2012) Oxidative stress in children with severe malaria. J Trop Pediatr 58:147–150. doi:10.1093/tropej/fmr043

    Article  PubMed  Google Scholar 

  67. Sohail M, Kaul A, Raziuddin M, Adak T (2007) Decreased glutathione-S-transferase activity: diagnostic and protective role in vivax malaria. Clin Biochem 40:377–382. doi:10.1016/j.clinbiochem.2007.01.005

    Article  CAS  PubMed  Google Scholar 

  68. Yazar S, Kilic E, Saraymen R, Ozbilge H (2004) Serum malondialdehyde levels in patients infected with Plasmodium vivax. West Indian Med J 53:147–149

    CAS  PubMed  Google Scholar 

  69. Atamna H, Ginsburg H (1993) Origin of reactive oxygen species in erythrocytes infected with Plasmodium falciparum. Mol Biochem Parasitol 61:231–241

    Article  CAS  PubMed  Google Scholar 

  70. Dondorp AM, Omodeo-Sale F, Chotivanich K, Taramelli D, White NJ (2003) Oxidative stress and rheology in severe malaria. Redox Rep 8(5):292–294. doi:10.1179/135100003225002934

    Article  CAS  PubMed  Google Scholar 

  71. Huber SM, Uhlemann A-C, Gamper NL, Duranton C, Kremsner PG, Lang F (2002) Plasmodium falciparum activates endogenous Cl– channels of human erythrocytes by membrane oxidation. EMBO J 21:22–30. doi:10.1093/emboj/21.1.22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Jaramillo M, Godbout M, Olivier M (2005) Hemozoin induces macrophage chemokine expression through oxidative stress-dependent and -independent mechanisms. J Immunol 174:475–484

    Article  CAS  PubMed  Google Scholar 

  73. Potter SM, Mitchell AJ, Cowden WB, Sanni LA, Dinauer M, de Haan JB, Hunt NH (2005) Phagocyte-derived reactive oxygen species do not influence the progression of murine blood-stage malaria infections. Infect Immun 73:4941–4947. doi:10.1128/IAI.73.8.4941-4947.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Iwalokun BA, Bamiro SB, Ogunledun A (2006) Levels and interactions of plasma xanthine oxidase, catalase and liver function parameters in Nigerian children with Plasmodium falciparum infection. APMIS 114(12):842–850

    Article  CAS  PubMed  Google Scholar 

  75. Das BS, Patnaik JK, Mohanty S, Mishra SK, Mohanty D, Satpathy SK, Bose TK (1993) Plasma antioxidants and lipid peroxidation products in falciparum malaria. Am J Trop Med Hyg 49(6):720–725

    CAS  PubMed  Google Scholar 

  76. Das BS, Thurnham DI, Patnaik JK, Das DB, Satpathy R, Bose TK (1990) Increased plasma lipid peroxidation in riboflavin-deficient, malaria-infected children. Am J Clin Nutr 51(5):859–863

    CAS  PubMed  Google Scholar 

  77. Isah MB, Ibrahim MA (2014) The role of antioxidants treatment on the pathogenesis of malarial infections: a review. Parasitol Res 113(3):801–809. doi:10.1007/s00436-014-3804-1

    Article  PubMed  Google Scholar 

  78. Lin JW, Spaccapelo R, Schwarzer E, Sajid M, Annoura T, Deroost K, Ravelli RB, Aime E, Capuccini B, Mommaas-Kienhuis AM, O’Toole T, Prins F, Franke-Fayard BM, Ramesar J, Chevalley-Maurel S, Kroeze H, Koster AJ, Tanke HJ, Crisanti A, Langhorne J, Arese P, Van den Steen PE, Janse CJ, Khan SM (2015) Replication of Plasmodium in reticulocytes can occur without hemozoin formation, resulting in chloroquine resistance. J Exp Med 212(6):893–903. doi:10.1084/jem.20141731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Pichyangkul S, Yongvanitchit K, Kum-arb U, Hemmi H, Akira S, Krieg AM, Heppner DG, Stewart VA, Hasegawa H, Looareesuwan S, Shanks GD, Miller RS (2004) Malaria blood stage parasites activate human plasmacytoid dendritic cells and murine dendritic cells through a Toll-like receptor 9-dependent pathway. J Immunol 172(8):4926–4933

    Article  CAS  PubMed  Google Scholar 

  80. Giusti P, Urban BC, Frascaroli G, Albrecht L, Tinti A, Troye-Blomberg M, Varani S (2011) Plasmodium falciparum-infected erythrocytes and beta-hematin induce partial maturation of human dendritic cells and increase their migratory ability in response to lymphoid chemokines. Infect Immun 79(7):2727–2736. doi:10.1128/IAI.00649-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Walther M, Woodruff J, Edele F, Jeffries D, Tongren JE, King E, Andrews L, Bejon P, Gilbert SC, De Souza JB, Sinden R, Hill AV, Riley EM (2006) Innate immune responses to human malaria: heterogeneous cytokine responses to blood-stage Plasmodium falciparum correlate with parasitological and clinical outcomes. J Immunol 177(8):5736–5745

    Article  CAS  PubMed  Google Scholar 

  82. Franklin BS, Parroche P, Ataide MA, Lauw F, Ropert C, de Oliveira RB, Pereira D, Tada MS, Nogueira P, da Silva LH, Bjorkbacka H, Golenbock DT, Gazzinelli RT (2009) Malaria primes the innate immune response due to interferon-gamma induced enhancement of toll-like receptor expression and function. Proc Natl Acad Sci U S A 106(14):5789–5794. doi:10.1073/pnas.0809742106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Miller JL, Sack BK, Baldwin M, Vaughan AM, Kappe SH (2014) Interferon-mediated innate immune responses against malaria parasite liver stages. Cell Rep 7(2):436–447. doi:10.1016/j.celrep.2014.03.018

    Article  CAS  PubMed  Google Scholar 

  84. Schofield L, Ferreira A, Altszuler R, Nussenzweig V, Nussenzweig RS (1987) Interferon-gamma inhibits the intrahepatocytic development of malaria parasites in vitro. J Immunol 139(6):2020–2025

    CAS  PubMed  Google Scholar 

  85. Vergara U, Ferreira A, Schellekens H, Nussenzweig V (1987) Mechanism of escape of exoerythrocytic forms (EEF) of malaria parasites from the inhibitory effects of interferon-gamma. J Immunol 138(12):4447–4449

    CAS  PubMed  Google Scholar 

  86. Abdalla SH (1988) Peripheral blood and bone marrow leucocytes in Gambian children with malaria: numerical changes and evaluation of phagocytosis. Ann Trop Paediatr 8(4):250–258

    Article  CAS  PubMed  Google Scholar 

  87. Mahanta A, Kar SK, Kakati S, Baruah S (2015) Heightened inflammation in severe malaria is associated with decreased IL-10 expression levels and neutrophils. Innate Immun 21(5):546–552. doi:10.1177/1753425914561277

    Article  CAS  PubMed  Google Scholar 

  88. Tangteerawatana P, Krudsood S, Kanchanakhan N, Troye-Blomberg M, Khusmith S (2014) Low monocyte to neutrophil ratio in peripheral blood associated with disease complication in primary Plasmodium falciparum infection. Southeast Asian J Trop Med Public Health 45(3):517–530

    CAS  PubMed  Google Scholar 

  89. Pierrot C, Adam E, Hot D, Lafitte S, Capron M, George JD, Khalife J (2007) Contribution of T cells and neutrophils in protection of young susceptible rats from fatal experimental malaria. J Immunol 178(3):1713–1722

    Article  CAS  PubMed  Google Scholar 

  90. Ioannidis LJ, Nie CQ, Ly A, Ryg-Cornejo V, Chiu CY, Hansen DS (2016) Monocyte- and neutrophil-derived CXCL10 impairs efficient control of blood-stage malaria infection and promotes severe disease. J Immunol 196(3):1227–1238. doi:10.4049/jimmunol.1501562

    Article  CAS  PubMed  Google Scholar 

  91. Schumak B, Klocke K, Kuepper JM, Biswas A, Djie-Maletz A, Limmer A, van Rooijen N, Mack M, Hoerauf A, Dunay IR (2015) Specific depletion of Ly6Chi inflammatory monocytes prevents immunopathology in experimental cerebral malaria. PLoS One 10(4), e0124080. doi:10.1371/journal.pone.0124080

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Feintuch CM, Saidi A, Seydel K, Chen G, Goldman-Yassen A, Mita-Mendoza NK, Kim RS, Frenette PS, Taylor T, Daily JP (2015) Activated neutrophils are associated with pediatric cerebral malaria vasculopathy in Malawian children. MBio 7(1):e01300–e01315. doi:10.1128/mBio.01300-15

    Google Scholar 

  93. Rocha BC, Marques PE, Leoratti FM, Junqueira C, Pereira DB, Antonelli LR, Menezes GB, Golenbock DT, Gazzinelli RT (2015) Type I interferon transcriptional signature in neutrophils and low-density granulocytes are associated with tissue damage in malaria. Cell Rep 13(12):2829–2841. doi:10.1016/j.celrep.2015.11.055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Leoratti FM, Trevelin SC, Cunha FQ, Rocha BC, Costa PA, Gravina HD, Tada MS, Pereira DB, Golenbock DT, Antonelli LR, Gazzinelli RT (2012) Neutrophil paralysis in Plasmodium vivax malaria. PLoS Negl Trop Dis 6(6), e1710. doi:10.1371/journal.pntd.0001710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Furuta T, Kikuchi T, Iwakura Y, Watanabe N (2006) Protective roles of mast cells and mast cell-derived TNF in murine malaria. J Immunol 177(5):3294–3302

    Article  CAS  PubMed  Google Scholar 

  96. Stevenson MM, Ghadirian E, Phillips NC, Rae D, Podoba JE (1989) Role of mononuclear phagocytes in elimination of Plasmodium chabaudi AS infection. Parasite Immunol 11(5):529–544

    Article  CAS  PubMed  Google Scholar 

  97. Couper KN, Blount DG, Hafalla JC, van Rooijen N, de Souza JB, Riley EM (2007) Macrophage-mediated but gamma interferon-independent innate immune responses control the primary wave of Plasmodium yoelii parasitemia. Infect Immun 75(12):5806–5818. doi:10.1128/IAI.01005-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Ayi K, Patel SN, Serghides L, Smith TG, Kain KC (2005) Nonopsonic phagocytosis of erythrocytes infected with ring-stage Plasmodium falciparum. Infect Immun 73(4):2559–2563. doi:10.1128/IAI.73.4.2559-2563.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Bettiol E, Van de Hoef DL, Carapau D, Rodriguez A (2010) Efficient phagosomal maturation and degradation of Plasmodium-infected erythrocytes by dendritic cells and macrophages. Parasite Immunol 32(6):389–398. doi:10.1111/j.1365-3024.2010.01198.x

    Article  CAS  PubMed  Google Scholar 

  100. Patel SN, Serghides L, Smith TG, Febbraio M, Silverstein RL, Kurtz TW, Pravenec M, Kain KC (2004) CD36 mediates the phagocytosis of Plasmodium falciparum-infected erythrocytes by rodent macrophages. J Infect Dis 189(2):204–213. doi:10.1086/380764

    Article  CAS  PubMed  Google Scholar 

  101. Su Z, Fortin A, Gros P, Stevenson MM (2002) Opsonin-independent phagocytosis: an effector mechanism against acute blood-stage Plasmodium chabaudi AS infection. J Infect Dis 186(9):1321–1329. doi:10.1086/344576

    Article  CAS  PubMed  Google Scholar 

  102. Fernandez-Arias C, Lopez JP, Hernandez-Perez JN, Bautista-Ojeda MD, Branch O, Rodriguez A (2013) Malaria inhibits surface expression of complement receptor 1 in monocytes/macrophages, causing decreased immune complex internalization. J Immunol 190(7):3363–3372. doi:10.4049/jimmunol.1103812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yoneto T, Waki S, Takai T, Tagawa Y, Iwakura Y, Mizuguchi J, Nariuchi H, Yoshimoto T (2001) A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the host resistance to blood-stage Plasmodium berghei XAT infection. J Immunol 166(10):6236–6241

    Article  CAS  PubMed  Google Scholar 

  104. Steinman RM (2012) Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 30:1–22. doi:10.1146/annurev-immunol-100311-102839

    Article  CAS  PubMed  Google Scholar 

  105. Elliott SR, Spurck TP, Dodin JM, Maier AG, Voss TS, Yosaatmadja F, Payne PD, McFadden GI, Cowman AF, Rogerson SJ, Schofield L, Brown GV (2007) Inhibition of dendritic cell maturation by malaria is dose dependent and does not require Plasmodium falciparum erythrocyte membrane protein 1. Infect Immun 75(7):3621–3632. doi:10.1128/IAI.00095-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Urban BC, Ferguson DJ, Pain A, Willcox N, Plebanski M, Austyn JM, Roberts DJ (1999) Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature 400(6739):73–77. doi:10.1038/21900

    Article  CAS  PubMed  Google Scholar 

  107. Teirlinck AC, McCall MB, Roestenberg M, Scholzen A, Woestenenk R, de Mast Q, van der Ven AJ, Hermsen CC, Luty AJ, Sauerwein RW (2011) Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans. PLoS Pathog 7(12), e1002389. doi:10.1371/journal.ppat.1002389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kho S, Marfurt J, Noviyanti R, Kusuma A, Piera KA, Burdam FH, Kenangalem E, Lampah DA, Engwerda CR, Poespoprodjo JR, Price RN, Anstey NM, Minigo G, Woodberry T (2015) Preserved dendritic cell HLA-DR expression and reduced regulatory T cell activation in asymptomatic Plasmodium falciparum and P. vivax infection. Infect Immun 83(8):3224–3232. doi:10.1128/IAI.00226-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Loughland JR, Minigo G, Burel J, Tipping PE, Piera KA, Amante FH, Engwerda CR, Good MF, Doolan DL, Anstey NM, McCarthy JS, Woodberry T (2016) Profoundly reduced CD1c+ myeloid dendritic cell HLA-DR and CD86 expression and increased TNF production in experimental human blood-stage malaria infection. Infect Immun 84(5):1403–1412. doi:10.1128/IAI.01522-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Urban BC, Mwangi T, Ross A, Kinyanjui S, Mosobo M, Kai O, Lowe B, Marsh K, Roberts DJ (2001) Peripheral blood dendritic cells in children with acute Plasmodium falciparum malaria. Blood 98(9):2859–2861

    Article  CAS  PubMed  Google Scholar 

  111. Mukherjee P, Chauhan VS (2008) Plasmodium falciparum-free merozoites and infected RBCs distinctly affect soluble CD40 ligand-mediated maturation of immature monocyte-derived dendritic cells. J Leukoc Biol 84(1):244–254. doi:10.1189/jlb.0807565

    Article  CAS  PubMed  Google Scholar 

  112. Gowda NM, Wu X, Kumar S, Febbraio M, Gowda DC (2013) CD36 contributes to malaria parasite-induced pro-inflammatory cytokine production and NK and T cell activation by dendritic cells. PLoS One 8(10), e77604. doi:10.1371/journal.pone.0077604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Woodberry T, Minigo G, Piera KA, Amante FH, Pinzon-Charry A, Good MF, Lopez JA, Engwerda CR, McCarthy JS, Anstey NM (2012) Low-level Plasmodium falciparum blood-stage infection causes dendritic cell apoptosis and dysfunction in healthy volunteers. J Infect Dis 206(3):333–340. doi:10.1093/infdis/jis366

    Article  CAS  PubMed  Google Scholar 

  114. Pinzon-Charry A, Woodberry T, Kienzle V, McPhun V, Minigo G, Lampah DA, Kenangalem E, Engwerda C, Lopez JA, Anstey NM, Good MF (2013) Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria. J Exp Med 210(8):1635–1646. doi:10.1084/jem.20121972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Urban BC, Cordery D, Shafi MJ, Bull PC, Newbold CI, Williams TN, Marsh K (2006) The frequency of BDCA3-positive dendritic cells is increased in the peripheral circulation of Kenyan children with severe malaria. Infect Immun 74(12):6700–6706. doi:10.1128/IAI.00861-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Teirlinck AC, Roestenberg M, Bijker EM, Hoffman SL, Sauerwein RW, Scholzen A (2015) Plasmodium falciparum infection of human volunteers activates monocytes and CD16+ dendritic cells and induces upregulation of CD16 and CD1c expression. Infect Immun 83(9):3732–3739. doi:10.1128/IAI.00473-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Artavanis-Tsakonas K, Eleme K, McQueen KL, Cheng NW, Parham P, Davis DM, Riley EM (2003) Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes. J Immunol 171(10):5396–5405

    Article  CAS  PubMed  Google Scholar 

  118. Horowitz A, Newman KC, Evans JH, Korbel DS, Davis DM, Riley EM (2010) Cross-talk between T cells and NK cells generates rapid effector responses to Plasmodium falciparum-infected erythrocytes. J Immunol 184(11):6043–6052. doi:10.4049/jimmunol.1000106

    Article  CAS  PubMed  Google Scholar 

  119. Stegmann KA, De Souza JB, Riley EM (2015) IL-18-induced expression of high-affinity IL-2R on murine NK cells is essential for NK-cell IFN-gamma production during murine Plasmodium yoelii infection. Eur J Immunol 45(12):3431–3440. doi:10.1002/eji.201546018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Newman KC, Korbel DS, Hafalla JC, Riley EM (2006) Cross-talk with myeloid accessory cells regulates human natural killer cell interferon-gamma responses to malaria. PLoS Pathog 2(12), e118. doi:10.1371/journal.ppat.0020118

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Kitaguchi T, Nagoya M, Amano T, Suzuki M, Minami M (1996) Analysis of roles of natural killer cells in defense against Plasmodium chabaudi in mice. Parasitol Res 82(4):352–357

    Article  CAS  PubMed  Google Scholar 

  122. Mohan K, Moulin P, Stevenson MM (1997) Natural killer cell cytokine production, not cytotoxicity, contributes to resistance against blood-stage Plasmodium chabaudi AS infection. J Immunol 159(10):4990–4998

    CAS  PubMed  Google Scholar 

  123. Roussilhon C, Agrapart M, Ballet JJ, Bensussan A (1990) T lymphocytes bearing the gamma delta T cell receptor in patients with acute Plasmodium falciparum malaria. J Infect Dis 162(1):283–285

    Article  CAS  PubMed  Google Scholar 

  124. Ho M, Webster HK, Tongtawe P, Pattanapanyasat K, Weidanz WP (1990) Increased gamma delta T cells in acute Plasmodium falciparum malaria. Immunol Lett 25(1-3):139–141

    Article  CAS  PubMed  Google Scholar 

  125. Behr C, Poupot R, Peyrat MA, Poquet Y, Constant P, Dubois P, Bonneville M, Fournie JJ (1996) Plasmodium falciparum stimuli for human gammadelta T cells are related to phosphorylated antigens of mycobacteria. Infect Immun 64(8):2892–2896

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Costa G, Loizon S, Guenot M, Mocan I, Halary F, de Saint-Basile G, Pitard V, Dechanet-Merville J, Moreau JF, Troye-Blomberg M, Mercereau-Puijalon O, Behr C (2011) Control of Plasmodium falciparum erythrocytic cycle: γδ T cells target the red blood cell-invasive merozoites. Blood 118(26):6952–6962. doi:10.1182/blood-2011-08-376111

    Article  CAS  PubMed  Google Scholar 

  127. D’Ombrain MC, Hansen DS, Simpson KM, Schofield L (2007) gammadelta-T cells expressing NK receptors predominate over NK cells and conventional T cells in the innate IFN-gamma response to Plasmodium falciparum malaria. Eur J Immunol 37(7):1864–1873. doi:10.1002/eji.200636889

    Article  PubMed  CAS  Google Scholar 

  128. Goodier MR, Lundqvist C, Hammarstrom ML, Troye-Blomberg M, Langhorne J (1995) Cytokine profiles for human V gamma 9+ T cells stimulated by Plasmodium falciparum. Parasite Immunol 17(8):413–423

    Article  CAS  PubMed  Google Scholar 

  129. Stanisic DI, Cutts J, Eriksson E, Fowkes FJ, Rosanas-Urgell A, Siba P, Laman M, Davis TM, Manning L, Mueller I, Schofield L (2014) gammadelta T cells and CD14+ monocytes are predominant cellular sources of cytokines and chemokines associated with severe malaria. J Infect Dis 210(2):295–305. doi:10.1093/infdis/jiu083

    Article  CAS  PubMed  Google Scholar 

  130. Jones SM, Goodier MR, Langhorne J (1996) The response of gamma delta T cells to Plasmodium falciparum is dependent on activated CD4+ T cells and the recognition of MHC class I molecules. Immunology 89(3):405–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Waterfall M, Black A, Riley E (1998) Gammadelta+ T cells preferentially respond to live rather than killed malaria parasites. Infect Immun 66(5):2393–2398

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Inoue S, Niikura M, Takeo S, Mineo S, Kawakami Y, Uchida A, Kamiya S, Kobayashi F (2012) Enhancement of dendritic cell activation via CD40 ligand-expressing gammadelta T cells is responsible for protective immunity to Plasmodium parasites. Proc Natl Acad Sci U S A 109(30):12129–12134. doi:10.1073/pnas.1204480109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Kobayashi F, Niikura M, Waki S, Matsui T, Fujino T, Tsuruhara T, Kamiya S (2007) Plasmodium berghei XAT: contribution of gammadelta T cells to host defense against infection with blood-stage nonlethal malaria parasite. Exp Parasitol 117(4):368–375. doi:10.1016/j.exppara.2007.05.002

    Article  CAS  PubMed  Google Scholar 

  134. Weidanz WP, LaFleur G, Brown A, Burns JM Jr, Gramaglia I, van der Heyde HC (2010) Gammadelta T cells but not NK cells are essential for cell-mediated immunity against Plasmodium chabaudi malaria. Infect Immun 78(10):4331–4340. doi:10.1128/IAI.00539-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Obiero JM, Shekalaghe S, Hermsen CC, Mpina M, Bijker EM, Roestenberg M, Teelen K, Billingsley PF, Sim BK, James ER, Daubenberger CA, Hoffman SL, Abdulla S, Sauerwein RW, Scholzen A (2015) Impact of malaria preexposure on antiparasite cellular and humoral immune responses after controlled human malaria infection. Infect Immun 83(5):2185–2196. doi:10.1128/IAI.03069-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Jagannathan P, Kim CC, Greenhouse B, Nankya F, Bowen K, Eccles-James I, Muhindo MK, Arinaitwe E, Tappero JW, Kamya MR, Dorsey G, Feeney ME (2014) Loss and dysfunction of Vdelta2+ gammadelta T cells are associated with clinical tolerance to malaria. Sci Transl Med 6(251):251ra117. doi:10.1126/scitranslmed.3009793

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Druilhe P, Rhodes-Feuillette A, Canivet M, Gentilini M, Periês J (1982) Circulating interferon in patients with Plasmodium falciparum, P. ovale and P. vivax malaria. Trans R Soc Trop Med Hyg 76:422–423

    Article  CAS  PubMed  Google Scholar 

  138. Ojo-Amaize EA, Salimonu LS, Williams AI, Akinwolere OA, Shabo R, Alm GV, Wigzell H (1981) Positive correlation between degree of parasitemia, interferon titers, and natural killer cell activity in Plasmodium falciparum-infected children. J Immunol 127:2296–2300

    CAS  PubMed  Google Scholar 

  139. Andrade BB, Reis-Filho A, Souza-Neto SM, Clarêncio J, Camargo LMA, Barral A, Barral-Netto M (2010) Severe Plasmodium vivax malaria exhibits marked inflammatory imbalance. Malar J 9:13. doi:10.1186/1475-2875-9-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Angulo I, Fresno M (2002) Cytokines in the pathogenesis of and protection against malaria. Clin Vaccine Immunol 9:1145–1152. doi:10.1128/CDLI.9.6.1145-1152.2002

    Article  CAS  Google Scholar 

  141. Grau GE, Taylor TE, Molyneux ME, Wirima JJ, Vassalli P, Hommel M, Lambert PH (1989) Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med 320:1586–1591. doi:10.1056/NEJM198906153202404

    Article  CAS  PubMed  Google Scholar 

  142. Kern P, Hemmer CJ, Van Damme J, Gruss HJ, Dietrich M (1989) Elevated tumor necrosis factor alpha and interleukin-6 serum levels as markers for complicated Plasmodium falciparum malaria. Am J Med 87:139–143

    Article  CAS  PubMed  Google Scholar 

  143. Kremsner PG, Winkler S, Brandts C, Wildling E, Jenne L, Graninger W, Prada J, Bienzle U, Juillard P, Grau GE (1995) Prediction of accelerated cure in Plasmodium falciparum malaria by the elevated capacity of tumor necrosis factor production. Am J Trop Med Hyg 53:532–538

    CAS  PubMed  Google Scholar 

  144. Kwiatkowski D, Sambou I, Twumasi P, Greenwood BM, Hill AVS, Manogue KR, Cerami A, Castracane J, Brewster DR (1990) TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336:1201–1204. doi:10.1016/0140-6736(90)92827-5

    Article  CAS  PubMed  Google Scholar 

  145. Lyke KE, Burges R, Cissoko Y, Sangare L, Dao M, Diarra I, Kone A, Harley R, Plowe CV, Doumbo OK, Sztein MB (2004) Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect Immun 72:5630–5637. doi:10.1128/IAI.72.10.5630-5637.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Mordmüller BG, Metzger WG, Juillard P, Brinkman BM, Verweij CL, Grau GE, Kremsner PG (1997) Tumor necrosis factor in Plasmodium falciparum malaria: high plasma level is associated with fever, but high production capacity is associated with rapid fever clearance. Eur Cytokine Netw 8:29–35

    PubMed  Google Scholar 

  147. Mshana RN, Boulandi J, Mshana NM, Mayombo J, Mendome G (1991) Cytokines in the pathogenesis of malaria: levels of IL-I beta, IL-4, IL-6, TNF-alpha and IFN-gamma in plasma of healthy individuals and malaria patients in a holoendemic area. J Clin Lab Immunol 34:131–139

    CAS  PubMed  Google Scholar 

  148. Ockenhouse CF, Hu W-c, Kester KE, Cummings JF, Stewart A, Heppner DG, Jedlicka AE, Scott AL, Wolfe ND, Vahey M, Burke DS (2006) Common and divergent immune response signaling pathways discovered in peripheral blood mononuclear cell gene expression patterns in presymptomatic and clinically apparent malaria. Infect Immun 74:5561–5573. doi:10.1128/IAI.00408-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Peyron F, Burdin N, Ringwald P, Vuillez JP, Rousset F, Banchereau J (1994) High levels of circulating IL-10 in human malaria. Clin Exp Immunol 95:300–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Ringwald P, Peyron F, Vuillez JP, Touze JE, Le Bras J, Deloron P (1991) Levels of cytokines in plasma during Plasmodium falciparum malaria attacks. J Clin Microbiol 29:2076–2078

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Brown H, Turner G, Rogerson S, Tembo M, Mwenechanya J, Molyneux M, Taylor T (1999) Cytokine expression in the brain in human cerebral malaria. J Infect Dis 180:1742–1746

    Article  CAS  PubMed  Google Scholar 

  152. Maneerat Y, Pongponratn E, Viriyavejakul P, Punpoowong B, Looareesuwan S, Udomsangpetch R (1999) Cytokines associated with pathology in the brain tissue of fatal malaria. Southeast Asian J Trop Med Public Health 30:643–649

    CAS  PubMed  Google Scholar 

  153. De Souza JB, Williamson KH, Otani T, Playfair JH (1997) Early gamma interferon responses in lethal and nonlethal murine blood-stage malaria. Infect Immun 65:1593–1598

    PubMed  PubMed Central  Google Scholar 

  154. Bate CA, Taverne J, Playfair JH (1988) Malarial parasites induce TNF production by macrophages. Immunology 64:227–231

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Clark IA, Hunt NH, Butcher GA, Cowden WB (1987) Inhibition of murine malaria (Plasmodium chabaudi) in vivo by recombinant interferon-gamma or tumor necrosis factor, and its enhancement by butylated hydroxyanisole. J Immunol 139:3493–3496

    CAS  PubMed  Google Scholar 

  156. Shear HL, Srinivasan R, Nolan T, Ng C (1989) Role of IFN-gamma in lethal and nonlethal malaria in susceptible and resistant murine hosts. J Immunol 143:2038–2044

    CAS  PubMed  Google Scholar 

  157. Taverne J, Tavernier J, Fiers W, Playfair JH (1987) Recombinant tumour necrosis factor inhibits malaria parasites in vivo but not in vitro. Clin Exp Immunol 67:1–4

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Rockett KA, Awburn MM, Aggarwal BB, Cowden WB, Clark IA (1992) In vivo induction of nitrite and nitrate by tumor necrosis factor, lymphotoxin, and interleukin-1: possible roles in malaria. Infect Immun 60:3725–3730

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Knight JC, Udalova I, Hill AV, Greenwood BM, Peshu N, Marsh K, Kwiatkowski D (1999) A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat Genet 22:145–150. doi:10.1038/9649

    Article  CAS  PubMed  Google Scholar 

  160. McGuire W, Hill AV, Allsopp CE, Greenwood BM, Kwiatkowski D (1994) Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature 371:508–510. doi:10.1038/371508a0

    Article  CAS  PubMed  Google Scholar 

  161. McGuire W, Knight JC, Hill AV, Allsopp CE, Greenwood BM, Kwiatkowski D (1999) Severe malarial anemia and cerebral malaria are associated with different tumor necrosis factor promoter alleles. J Infect Dis 179:287–290. doi:10.1086/314533

    Article  CAS  PubMed  Google Scholar 

  162. Ribeiro BP, Cassiano GC, de Souza RM, Cysne DN, Grisotto MAG, de Azevedo Dos Santos APS, Marinho CRF, Machado RLD, Nascimento FRF (2016) Polymorphisms in Plasmodium vivax circumsporozoite protein (CSP) influence parasite burden and cytokine balance in a pre-amazon endemic area from Brazil. PLoS Negl Trop Dis 10, e0004479. doi:10.1371/journal.pntd.0004479

    Article  PubMed Central  Google Scholar 

  163. Wattavidanage J, Carter R, Perera KL, Munasingha A, Bandara S, McGuinness D, Wickramasinghe AR, Alles HK, Mendis KN, Premawansa S (1999) TNFα*2 marks high risk of severe disease during Plasmodium falciparum malaria and other infections in Sri Lankans. Clin Exp Immunol 115:350–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. van Hensbroek MB, Palmer A, Onyiorah E, Schneider G, Jaffar S, Dolan G, Memming H, Frenkel J, Enwere G, Bennett S, Kwiatkowski D, Greenwood B (1996) The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria. J Infect Dis 174:1091–1097. doi:10.1093/infdis/174.5.1091

    Article  PubMed  Google Scholar 

  165. Deloron P, Chougnet C, Lepers JP, Tallet S, Coulanges P (1991) Protective value of elevated levels of gamma interferon in serum against exoerythrocytic stages of Plasmodium falciparum. J Clin Microbiol 29:1757–1760

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Hoffman SL, Crutcher JM, Puri SK, Ansari AA, Villinger F, Franke ED, Singh PP, Finkelman F, Gately MK, Dutta GP, Sedegah M (1997) Sterile protection of monkeys against malaria after administration of interleukin-12. Nat Med 3:80–83

    Article  CAS  PubMed  Google Scholar 

  167. Bienzle U, Fritsch KG, Hoth G, Rozdzinski E, Köhler K, Kalinowski M, Kremsner P, Rosenkaimer F, Feldmeier H (1988) Inhibition of Plasmodium vinckei-malaria in mice by recombinant murine interferon-gamma. Acta Trop 45:289–290

    CAS  PubMed  Google Scholar 

  168. Favre N, Ryffel B, Bordmann G, Rudin W (1997) The course of Plasmodium chabaudi chabaudi infections in interferon-gamma receptor deficient mice. Parasite Immunol 19:375–383

    Article  CAS  PubMed  Google Scholar 

  169. Huang KY, Schultz WW, Gordon FB (1968) Interferon induced by Plasmodium berghei. Science 162:123–124

    Article  CAS  PubMed  Google Scholar 

  170. Jahiel RI, Nussenzweig RS, Vilcek J, Vanderberg J (1969) Protective effect of interferon inducers on Plasmodium berghei malaria. Am J Trop Med Hyg 18:823–835

    CAS  PubMed  Google Scholar 

  171. Kobayashi F, Ishida H, Matsui T, Tsuji M (2000) Effects of in vivo administration of anti-IL-10 or anti-IFN-gamma monoclonal antibody on the host defense mechanism against Plasmodium yoelii yoelii infection. J Vet Med Sci 62:583–587

    Article  CAS  PubMed  Google Scholar 

  172. Meding SJ, Cheng SC, Simon-Haarhaus B, Langhorne J (1990) Role of gamma interferon during infection with Plasmodium chabaudi chabaudi. Infect Immun 58:3671–3678

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Schultz WW, Huang KY, Gordon FB (1968) Role of interferon in experimental mouse malaria. Nature 220:709–710

    Article  CAS  PubMed  Google Scholar 

  174. Stevenson MM, Tam MF, Nowotarski M (1990) Role of interferon-gamma and tumor necrosis factor in host resistance to Plasmodium chabaudi AS. Immunol Lett 25:115–121

    Article  CAS  PubMed  Google Scholar 

  175. Su Z, Stevenson MM (2000) Central role of endogenous gamma interferon in protective immunity against blood-stage Plasmodium chabaudi AS infection. Infect Immun 68:4399–4406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Sam H, Stevenson MM (1999) In vivo IL-12 production and IL-12 receptors beta1 and beta2 mRNA expression in the spleen are differentially up-regulated in resistant B6 and susceptible A/J mice during early blood-stage Plasmodium chabaudi AS malaria. J Immunol 162:1582–1589

    CAS  PubMed  Google Scholar 

  177. Singh RP, S-i K, Rao P, Okamura H, Mukherjee A, Chauhan VS (2002) The role of IL-18 in blood-stage immunity against murine malaria Plasmodium yoelii 265 and Plasmodium berghei ANKA. J Immunol 168:4674–4681

    Article  CAS  PubMed  Google Scholar 

  178. Stevenson MM, Tam MF, Wolf SF, Sher A (1995) IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-gamma and TNF-alpha and occurs via a nitric oxide-dependent mechanism. J Immunol 155:2545–2556

    CAS  PubMed  Google Scholar 

  179. Adachi K, Tsutsui H, Kashiwamura S, Seki E, Nakano H, Takeuchi O, Takeda K, Okumura K, Van Kaer L, Okamura H, Akira S, Nakanishi K (2001) Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. J Immunol 167:5928–5934

    Article  CAS  PubMed  Google Scholar 

  180. Yoshimoto T, Takahama Y, Wang CR, Yoneto T, Waki S, Nariuchi H (1998) A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection. J Immunol 160:5500–5505

    CAS  PubMed  Google Scholar 

  181. Ho M, Sexton MM, Tongtawe P, Looareesuwan S, Suntharasamai P, Webster HK (1995) Interleukin-10 inhibits tumor necrosis factor production but not antigen-specific lymphoproliferation in acute Plasmodium falciparum malaria. J Infect Dis 172:838–844

    Article  CAS  PubMed  Google Scholar 

  182. Luty AJ, Perkins DJ, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, Matousek P, Herbich K, Schmid D, Weinberg JB, Kremsner PG (2000) Low interleukin-12 activity in severe Plasmodium falciparum malaria. Infect Immun 68:3909–3915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Day NP, Hien TT, Schollaardt T, Loc PP, Chuong LV, Chau TT, Mai NT, Phu NH, Sinh DX, White NJ, Ho M (1999) The prognostic and pathophysiologic role of pro- and antiinflammatory cytokines in severe malaria. J Infect Dis 180:1288–1297. doi:10.1086/315016

    Article  CAS  PubMed  Google Scholar 

  184. Perkins DJ, Weinberg JB, Kremsner PG (2000) Reduced interleukin-12 and transforming growth factor-beta1 in severe childhood malaria: relationship of cytokine balance with disease severity. J Infect Dis 182:988–992. doi:10.1086/315762

    Article  CAS  PubMed  Google Scholar 

  185. Kurtzhals JA, Adabayeri V, Goka BQ, Akanmori BD, Oliver-Commey JO, Nkrumah FK, Behr C, Hviid L (1998) Low plasma concentrations of interleukin 10 in severe malarial anaemia compared with cerebral and uncomplicated malaria. Lancet 351:1768–1772. doi:10.1016/S0140-6736(97)09439-7

    Article  CAS  PubMed  Google Scholar 

  186. May J, Lell B, Luty AJ, Meyer CG, Kremsner PG (2000) Plasma interleukin-10: tumor necrosis factor (TNF)-alpha ratio is associated with TNF promoter variants and predicts malarial complications. J Infect Dis 182:1570–1573. doi:10.1086/315857

    Article  CAS  PubMed  Google Scholar 

  187. Othoro C, Lal AA, Nahlen B, Koech D, Orago AS, Udhayakumar V (1999) A low interleukin-10 tumor necrosis factor-alpha ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya. J Infect Dis 179:279–282. doi:10.1086/314548

    Article  CAS  PubMed  Google Scholar 

  188. Ouma C, Davenport GC, Were T, Otieno MF, Hittner JB, Vulule JM, Martinson J, Ong’echa JM, Ferrell RE, Perkins DJ (2008) Haplotypes of IL-10 promoter variants are associated with susceptibility to severe malarial anemia and functional changes in IL-10 production. Hum Genet 124:515–524. doi:10.1007/s00439-008-0578-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Hugosson E, Montgomery SM, Premji Z, Troye-Blomberg M, Björkman A (2004) Higher IL-10 levels are associated with less effective clearance of Plasmodium falciparum parasites. Parasite Immunol 26:111–117. doi:10.1111/j.0141-9838.2004.00678.x

    Article  CAS  PubMed  Google Scholar 

  190. Zeyrek FY, Kurcer MA, Zeyrek D, Simsek Z (2006) Parasite density and serum cytokine levels in Plasmodium vivax malaria in Turkey. Parasite Immunol 28:201–207. doi:10.1111/j.1365-3024.2006.00822.x

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY, USA

    Anton Götz, Maureen Ty & Ana Rodriguez

  2. Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal

    Angelo Ferreira Chora, Vanessa Zuzarte-Luís & Maria M. Mota

Authors
  1. Anton Götz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maureen Ty
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Angelo Ferreira Chora
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vanessa Zuzarte-Luís
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria M. Mota
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ana Rodriguez .

Editor information

Editors and Affiliations

  1. Instituto de Medicina Molecular, Faculdade de Medicina Universidade de Lisboa, Lisbon, Portugal

    Maria M. Mota

  2. Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, New York, USA

    Ana Rodriguez

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Götz, A., Ty, M., Chora, A.F., Zuzarte-Luís, V., Mota, M.M., Rodriguez, A. (2017). Innate Immunity to Malaria. In: Mota, M., Rodriguez, A. (eds) Malaria. Springer, Cham. https://doi.org/10.1007/978-3-319-45210-4_1

Download citation

Publish with us

Policies and ethics

Search

Navigation