Mammalian Genome

, Volume 22, Issue 1–2, pp 32–42 | Cite as

Host resistance to malaria: using mouse models to explore the host response

  • Rhea Longley
  • Clare Smith
  • Anny Fortin
  • Joanne Berghout
  • Brendan McMorran
  • Gaétan Burgio
  • Simon FooteEmail author
  • Philippe Gros


Malaria is a disease that infects over 500 million people, causing at least 1 million deaths every year, with the majority occurring in developing countries. The current antimalarial arsenal is becoming dulled due to the rapid rate of resistance of the parasite. However, in populations living in malaria-endemic regions there are many examples of genetic-based resistance to the severe effects of the parasite Plasmodium. Defining the genetic factors behind host resistance has been an area of great scientific interest over the last few decades; this review summarizes the current knowledge of the genetic loci involved. Perhaps the lessons learned from the natural variation in both the human populations and experimental mouse models of infection may pave the way for novel resistance-proof antimalarials.


Malaria Artemisinin Cerebral Malaria Experimental Cerebral Malaria Advanced Intercross Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Amani V, Vigario AM, Belnoue E, Marussig M, Fonseca L et al (2000) Involvement of IFN-gamma receptor-mediated signaling in pathology and anti-malarial immunity induced by Plasmodium berghei infection. Eur J Immunol 30:1646–1655PubMedGoogle Scholar
  2. Amante FH, Stanley AC, Randall LM, Zhou Y, Haque A et al (2007) A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. Am J Pathol 171:548–559PubMedGoogle Scholar
  3. Ayi K, Turrini F, Piga A, Arese P (2004) Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait. Blood 104:3364–3371PubMedGoogle Scholar
  4. Ayi K, Min-Oo G, Serghides L, Crockett M, Kirby-Allen M et al (2008) Pyruvate kinase deficiency and malaria. N Engl J Med 358:1805–1810PubMedGoogle Scholar
  5. Bagot S, Campino S, Penha-Goncalves C, Pied S, Cazenave PA et al (2002) Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain. Proc Natl Acad Sci USA 99:9919–9923PubMedGoogle Scholar
  6. Beghdadi W, Porcherie A, Schneider BS, Dubayle D, Peronet R et al (2008) Inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease. J Exp Med 205:395–408PubMedGoogle Scholar
  7. Belnoue E, Kayibanda M, Deschemin JC, Viguier M, Mack M et al (2003) CCR5 deficiency decreases susceptibility to experimental cerebral malaria. Blood 101:4253–4259PubMedGoogle Scholar
  8. Berghout J, Min-Oo G, Tam M, Gauthier S, Stevenson MM et al (2009) Identification of a novel cerebral malaria susceptibility locus (Berr5) on mouse chromosome 19. Genes Immun 11:310–318PubMedGoogle Scholar
  9. Bongfen SE, Laroque A, Berghout J, Gros P (2009) Genetic and genomic analyses of host-pathogen interactions in malaria. Trends Parasitol 25:417–422PubMedGoogle Scholar
  10. Brand V, Koka S, Lang C, Jendrossek V, Huber SM et al (2008) Influence of amitriptyline on eryptosis, parasitemia and survival of Plasmodium berghei-infected mice. Cell Physiol Biochem 22:405–412PubMedGoogle Scholar
  11. Bullen DV, Hansen DS, Siomos MA, Schofield L, Alexander WS et al (2003) The lack of suppressor of cytokine signalling-1 (SOCS1) protects mice from the development of cerebral malaria caused by Plasmodium berghei ANKA. Parasite Immunol 25:113–118PubMedGoogle Scholar
  12. Burt RA, Baldwin TM, Marshall VM, Foote SJ (1999) Temporal expression of an H2-linked locus in host response to mouse malaria. Immunogenetics 50:278–285PubMedGoogle Scholar
  13. Campanella GS, Tager AM, El Khoury JK, Thomas SY, Abrazinski TA et al (2008) Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proc Natl Acad Sci USA 105:4814–4819PubMedGoogle Scholar
  14. Campino S, Bagot S, Bergman ML, Almeida P, Sepulveda N et al (2005) Genetic control of parasite clearance leads to resistance to Plasmodium berghei ANKA infection and confers immunity. Genes Immun 6:416–421PubMedGoogle Scholar
  15. Carvalho LJ (2010) Murine cerebral malaria: how far from human cerebral malaria? Trends Parasitol 26:271–272PubMedGoogle Scholar
  16. Coban C, Ishii KJ, Uematsu S, Arisue N, Sato S et al (2007) Pathological role of Toll-like receptor signaling in cerebral malaria. Int Immunol 19:67–79PubMedGoogle Scholar
  17. Combes V, Rosenkranz AR, Redard M, Pizzolato G, Lepidi H et al (2004) Pathogenic role of P-selectin in experimental cerebral malaria: importance of the endothelial compartment. Am J Pathol 164:781–786PubMedGoogle Scholar
  18. Combes V, Coltel N, Alibert M, van Eck M, Raymond C et al (2005) ABCA1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology. Am J Pathol 166:295–302PubMedGoogle Scholar
  19. Cox D, McConkey S (2010) The role of platelets in the pathogenesis of cerebral malaria. Cell Mol Life Sci 67:557–568PubMedGoogle Scholar
  20. Cunha-Rodrigues M, Portugal S, Febbraio M, Mota MM (2006) Infection by and protective immune responses against Plasmodium berghei ANKA are not affected in macrophage scavenger receptors A deficient mice. BMC Microbiol 6:73PubMedGoogle Scholar
  21. Darvasi A, Soller M (1995) Advanced intercross lines, an experimental population for fine genetic mapping. Genetics 141:1199–1207PubMedGoogle Scholar
  22. de Souza JB, Hafalla JC, Riley EM, Couper KN (2010) Cerebral malaria: why experimental murine models are required to understand the pathogenesis of disease. Parasitology 137:755–772PubMedGoogle Scholar
  23. Delahaye NF, Coltel N, Puthier D, Flori L, Houlgatte R et al (2006) Gene-expression profiling discriminates between cerebral malaria (CM)-susceptible mice and CM-resistant mice. J Infect Dis 193:312–321PubMedGoogle Scholar
  24. Delic D, Warskulat U, Borsch E, Al-Qahtani S, Al-Quraishi S et al (2010) Loss of ability to self-heal malaria upon taurine transporter deletion. Infect Immun 78:1642–1649PubMedGoogle Scholar
  25. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP et al (2009) Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361:455–467PubMedGoogle Scholar
  26. Engwerda CR, Mynott TL, Sawhney S, De Souza JB, Bickle QD et al (2002) Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principal mediator of murine cerebral malaria. J Exp Med 195:1371–1377PubMedGoogle Scholar
  27. Evans KJ, Hansen DS, van Rooijen N, Buckingham LA, Schofield L (2006) Severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes. Blood 107:1192–1199PubMedGoogle Scholar
  28. Finney CA, Lu Z, LeBourhis L, Philpott DJ, Kain KC (2009) Disruption of Nod-like receptors alters inflammatory response to infection but does not confer protection in experimental cerebral malaria. Am J Trop Med Hyg 80:718–722PubMedGoogle Scholar
  29. Flint J, Hill AV, Bowden DK, Oppenheimer SJ, Sill PR et al (1986) High frequencies of alpha-thalassaemia are the result of natural selection by malaria. Nature 321:744–750PubMedGoogle Scholar
  30. Foote SJ, Burt RA, Baldwin TM, Presente A, Roberts AW et al (1997) Mouse loci for malaria-induced mortality and the control of parasitaemia. Nat Genet 17:380–381PubMedGoogle Scholar
  31. Fortin A, Belouchi A, Tam MF, Cardon L, Skamene E et al (1997) Genetic control of blood parasitaemia in mouse malaria maps to chromosome 8. Nat Genet 17:382–383PubMedGoogle Scholar
  32. Fortin A, Cardon LR, Tam M, Skamene E, Stevenson MM et al (2001) Identification of a new malaria susceptibility locus (Char4) in recombinant congenic strains of mice. Proc Natl Acad Sci USA 98:10793–10798PubMedGoogle Scholar
  33. Fortin A, Stevenson MM, Gros P (2002) Complex genetic control of susceptibility to malaria in mice. Genes Immun 3:177–186PubMedGoogle Scholar
  34. Francischetti IM (2008) Does activation of the blood coagulation cascade have a role in malaria pathogenesis? Trends Parasitol 24:258–263PubMedGoogle Scholar
  35. Friedman MJ (1978) Erythrocytic mechanism of sickle cell resistance to malaria. Proc Natl Acad Sci USA 75:1994–1997PubMedGoogle Scholar
  36. Gramaglia I, Sobolewski P, Meays D, Contreras R, Nolan JP et al (2006) Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria. Nat Med 12:1417–1422PubMedGoogle Scholar
  37. Greenberg J, Nadel EM, Coatney GR (1954) Differences in survival of several inbred strains of mice and their hybrids infected with Plasmodium berghei. J Infect Dis 95:114–116PubMedGoogle Scholar
  38. Haldane JBS (1949) The rate of mutation of human genes. Proceedings of the Eighth International Congress of Genetics. Hereditas 35:267–273Google Scholar
  39. Hansen AM, Ball HJ, Mitchell AJ, Miu J, Takikawa O et al (2004) Increased expression of indoleamine 2,3-dioxygenase in murine malaria infection is predominantly localised to the vascular endothelium. Int J Parasitol 34:1309–1319PubMedGoogle Scholar
  40. Hansen DS, Siomos MA, Buckingham L, Scalzo AA, Schofield L (2003) Regulation of murine cerebral malaria pathogenesis by CD1d-restricted NKT cells and the natural killer complex. Immunity 18:391–402PubMedGoogle Scholar
  41. Herbas MS, Okazaki M, Terao E, Xuan X, Arai H et al (2010) alpha-Tocopherol transfer protein inhibition is effective in the prevention of cerebral malaria in mice. Am J Clin Nutr 91:200–207PubMedGoogle Scholar
  42. Hernandez-Valladares M, Naessens J, Gibson JP, Musoke AJ, Nagda S et al (2004a) Confirmation and dissection of QTL controlling resistance to malaria in mice. Mamm Genome 15:390–398PubMedGoogle Scholar
  43. Hernandez-Valladares M, Rihet P, Ole-MoiYoi OK, Iraqi FA (2004b) Mapping of a new quantitative trait locus for resistance to malaria in mice by a comparative mapping approach with human Chromosome 5q31–q33. Immunogenetics 56:115–117PubMedGoogle Scholar
  44. Hernandez-Valladares M, Naessens J, Iraqi FA (2005) Genetic resistance to malaria in mouse models. Trends Parasitol 21:352–355PubMedGoogle Scholar
  45. Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P et al (1991) Common west African HLA antigens are associated with protection from severe malaria. Nature 352:595–600PubMedGoogle Scholar
  46. Hisaeda H, Tetsutani K, Imai T, Moriya C, Tu L et al (2008) Malaria parasites require TLR9 signaling for immune evasion by activating regulatory T cells. J Immunol 180:2496–2503PubMedGoogle Scholar
  47. Huber SM, Duranton C, Henke G, Van De Sand C, Heussler V et al (2004) Plasmodium induces swelling-activated ClC-2 anion channels in the host erythrocyte. J Biol Chem 279:41444–41452PubMedGoogle Scholar
  48. Hunt NH, Driussi C, Sai-Kiang L (2001) Haptoglobin and malaria. Redox Rep 6:389–392PubMedGoogle Scholar
  49. Hunt NH, Golenser J, Chan-Ling T, Parekh S, Rae C et al (2006) Immunopathogenesis of cerebral malaria. Int J Parasitol 36:569–582PubMedGoogle Scholar
  50. Hunt NH, Grau GE, Engwerda C, Barnum SR, van der Heyde H et al (2010) Murine cerebral malaria: the whole story. Trends Parasitol 26:272–274PubMedGoogle Scholar
  51. Ing R, Gros P, Stevenson MM (2005) Interleukin-15 enhances innate and adaptive immune responses to blood-stage malaria infection in mice. Infect Immun 73:3172–3177PubMedGoogle Scholar
  52. Ishikawa S, Uozumi N, Shiibashi T, Izumi T, Fukayama M et al (2004) Short report: Lethal malaria in cytosolic phospholipase A2- and phospholipase A2IIA-deficient mice. Am J Trop Med Hyg 70:645–650PubMedGoogle Scholar
  53. Jallow M, Teo YY, Small KS, Rockett KA, Deloukas P et al (2009) Genome-wide and fine-resolution association analysis of malaria in West Africa. Nat Genet 41(6):657–665PubMedGoogle Scholar
  54. Jarolim P, Palek J, Amato D, Hassan K, Sapak P et al (1991) Deletion in erythrocyte band 3 gene in malaria-resistant Southeast Asian ovalocytosis. Proc Natl Acad Sci USA 88:11022–11026PubMedGoogle Scholar
  55. Kwiatkowski DP, Luoni G (2006) Host genetic factors in resistance and susceptibility to malaria. Parassitologia 48:450–467PubMedGoogle Scholar
  56. Lamb TJ, Brown DE, Potocnik AJ, Langhorne J (2006) Insights into the immunopathogenesis of malaria using mouse models. Expert Rev Mol Med 8:1–22PubMedGoogle Scholar
  57. Li J, Chang WL, Sun G, Chen HL, Specian RD et al (2003) Intercellular adhesion molecule 1 is important for the development of severe experimental malaria but is not required for leukocyte adhesion in the brain. J Investig Med 51:128–140PubMedGoogle Scholar
  58. Lin E, Pappenfuss T, Tan RB, Senyschyn D, Bahlo M et al (2006) Mapping of the Plasmodium chabaudi resistance locus char2. Infect Immun 74:5814–5819PubMedGoogle Scholar
  59. Lovegrove FE, Gharib SA, Patel SN, Hawkes CA, Kain KC et al (2007) Expression microarray analysis implicates apoptosis and interferon-responsive mechanisms in susceptibility to experimental cerebral malaria. Am J Pathol 171:1894–1903PubMedGoogle Scholar
  60. McDevitt MA, Xie J, Shanmugasundaram G, Griffith J, Liu A et al (2006) A critical role for the host mediator macrophage migration inhibitory factor in the pathogenesis of malarial anemia. J Exp Med 203:1185–1196PubMedGoogle Scholar
  61. 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 371:508–510PubMedGoogle Scholar
  62. Menard D, Barnadas C, Bouchier C, Henry-Halldin C, Gray LR et al (2010) Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proc Natl Acad Sci USA 107:5967–5971PubMedGoogle Scholar
  63. Min-Oo G, Fortin A, Tam MF, Nantel A, Stevenson MM et al (2003) Pyruvate kinase deficiency in mice protects against malaria. Nat Genet 35:357–362PubMedGoogle Scholar
  64. Min-Oo G, Fortin A, Tam MF, Gros P, Stevenson MM (2004) Phenotypic expression of pyruvate kinase deficiency and protection against malaria in a mouse model. Genes Immun 5:168–175PubMedGoogle Scholar
  65. Min-Oo G, Fortin A, Pitari G, Tam M, Stevenson MM et al (2007a) Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus. J Exp Med 204:511–524PubMedGoogle Scholar
  66. Min-Oo G, Tam M, Stevenson MM, Gros P (2007b) Pyruvate kinase deficiency: correlation between enzyme activity, extent of hemolytic anemia and protection against malaria in independent mouse mutants. Blood Cells Mol Dis 39:63–69PubMedGoogle Scholar
  67. Min-Oo G, Willemetz A, Tam M, Canonne-Hergaux F, Stevenson MM et al (2010) Mapping of Char10, a novel malaria susceptibility locus on mouse chromosome 9. Genes Immun 11:113–123PubMedGoogle Scholar
  68. Mishra SK, Newton CR (2009) Diagnosis and management of the neurological complications of falciparum malaria. Nat Rev Neurol 5:189–198PubMedGoogle Scholar
  69. Miu J, Mitchell AJ, Muller M, Carter SL, Manders PM et al (2008) Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency. J Immunol 180:1217–1230PubMedGoogle Scholar
  70. Mullerova J, Hozak P (2004) Use of recombinant congenic strains in mapping disease-modifying genes. News Physiol Sci 19:105–109PubMedGoogle Scholar
  71. Nagayasu E, Nagakura K, Akaki M, Tamiya G, Makino S et al (2002) Association of a determinant on mouse chromosome 18 with experimental severe Plasmodium berghei malaria. Infect Immun 70:512–516PubMedGoogle Scholar
  72. Nielsen PJ, Lorenz B, Muller AM, Wenger RH, Brombacher F et al (1997) Altered erythrocytes and a leaky block in B-cell development in. Blood 89:1058–1067PubMedGoogle Scholar
  73. Oakley MS, Majam V, Mahajan B, Gerald N, Anantharaman V et al (2009) Pathogenic roles of CD14, galectin-3, and OX40 during experimental cerebral malaria in mice. PLoS One 4:e6793PubMedGoogle Scholar
  74. Ohno T, Nishimura M (2004) Detection of a new cerebral malaria susceptibility locus, using CBA mice. Immunogenetics 56:675–678PubMedGoogle Scholar
  75. Ohno T, Ishih A, Kohara Y, Yonekawa H, Terada M et al (2001) Chromosomal mapping of the host resistance locus to rodent malaria (Plasmodium yoelii) infection in mice. Immunogenetics 53:736–740PubMedGoogle Scholar
  76. Ohno T, Kobayashi F, Nishimura M (2005) Fas has a role in cerebral malaria, but not in proliferation or exclusion of the murine parasite in mice. Immunogenetics 57:293–296PubMedGoogle Scholar
  77. Pamplona A, Ferreira A, Balla J, Jeney V, Balla G et al (2007) Heme oxygenase-1 and carbon monoxide suppress the pathogenesis of experimental cerebral malaria. Nat Med 13:703–710PubMedGoogle Scholar
  78. Patel SN, Berghout J, Lovegrove FE, Ayi K, Conroy A et al (2008) C5 deficiency and C5a or C5aR blockade protects against cerebral malaria. J Exp Med 205:1133–1143PubMedGoogle Scholar
  79. Pennacchio LA (2003) Insights from human/mouse genome comparisons. Mamm Genome 14:429–436PubMedGoogle Scholar
  80. Piguet PF, Da Laperrousaz C, Vesin C, Tacchini-Cottier F, Senaldi G et al (2000) Delayed mortality and attenuated thrombocytopenia associated with severe malaria in urokinase- and urokinase receptor-deficient mice. Infect Immun 68:3822–3829PubMedGoogle Scholar
  81. Piguet PF, Kan CD, Vesin C (2002) Role of the tumor necrosis factor receptor 2 (TNFR2) in cerebral malaria in mice. Lab Invest 82:1155–1166PubMedGoogle Scholar
  82. Piguet PF, Kan CD, Vesin C, Rochat A, Donati Y et al (2001) Role of CD40-CVD40L in mouse severe malaria. Am J Pathol 159:733–742PubMedGoogle Scholar
  83. Potter S, Chan-Ling T, Ball HJ, Mansour H, Mitchell A et al (2006) Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria. Int J Parasitol 36:485–496PubMedGoogle Scholar
  84. Potter SM, Mitchell AJ, Cowden WB, Sanni LA, Dinauer M et al (2005) Phagocyte-derived reactive oxygen species do not influence the progression of murine blood-stage malaria infections. Infect Immun 73:4941–4947PubMedGoogle Scholar
  85. Rank G, Sutton R, Marshall V, Lundie RJ, Caddy J et al (2009) Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant. Blood 113(14):3352–3362PubMedGoogle Scholar
  86. Reimer T, Shaw MH, Franchi L, Coban C, Ishii KJ et al (2010) Experimental cerebral malaria progresses independently of the Nlrp3 inflammasome. Eur J Immunol 40:764–769PubMedGoogle Scholar
  87. Renia L, Gruner AC, Snounou G (2010) Cerebral malaria: in praise of epistemes. Trends Parasitol 26:275–277PubMedGoogle Scholar
  88. Riley EM, Couper KN, Helmby H, Hafalla JC, de Souza JB et al (2010) Neuropathogenesis of human and murine malaria. Trends Parasitol 26:277–278PubMedGoogle Scholar
  89. Riopel J, Tam M, Mohan K, Marino MW, Stevenson MM (2001) Granulocyte-macrophage colony-stimulating factor-deficient mice have impaired resistance to blood-stage malaria. Infect Immun 69:129–136PubMedGoogle Scholar
  90. Ruwende C, Hill A (1998) Glucose-6-phosphate dehydrogenase deficiency and malaria. J Mol Med 76:581–588PubMedGoogle Scholar
  91. Saeftel M, Krueger A, Arriens S, Heussler V, Racz P et al (2004) Mice deficient in interleukin-4 (IL-4) or IL-4 receptor alpha have higher resistance to sporozoite infection with Plasmodium berghei (ANKA) than do naive wild-type mice. Infect Immun 72:322–331PubMedGoogle Scholar
  92. Sanni LA, Jarra W, Li C, Langhorne J (2004) Cerebral edema and cerebral hemorrhages in interleukin-10-deficient mice infected with Plasmodium chabaudi. Infect Immun 72:3054–3058PubMedGoogle Scholar
  93. Senaldi G, Shaklee CL, Guo J, Martin L, Boone T et al (1999) Protection against the mortality associated with disease models mediated by TNF and IFN-gamma in mice lacking IFN regulatory factor-1. J Immunol 163:6820–6826PubMedGoogle Scholar
  94. Sexton AC, Good RT, Hansen DS, D’Ombrain MC, Buckingham L et al (2004) Transcriptional profiling reveals suppressed erythropoiesis, up-regulated glycolysis, and interferon-associated responses in murine malaria. J Infect Dis 189:1245–1256PubMedGoogle Scholar
  95. Shear HL, Roth E Jr, Ng C, Nagel RL (1991) Resistance to malaria in ankyrin and spectrin deficient mice. Br J Haematol 78:555–560PubMedGoogle Scholar
  96. Srivastava K, Cockburn IA, Swaim A, Thompson LE, Tripathi A et al (2008) Platelet factor 4 mediates inflammation in experimental cerebral malaria. Cell Host Microbe 4:179–187PubMedGoogle Scholar
  97. Stevenson MM, Gros P, Olivier M, Fortin A, Serghides L (2010) Cerebral malaria: human versus mouse studies. Trends Parasitol 26:274–275PubMedGoogle Scholar
  98. Stoelcker B, Hehlgans T, Weigl K, Bluethmann H, Grau GE et al (2002) Requirement for tumor necrosis factor receptor 2 expression on vascular cells to induce experimental cerebral malaria. Infect Immun 70:5857–5859PubMedGoogle Scholar
  99. Togbe D, Schofield L, Grau GE, Schnyder B, Boissay V et al (2007) Murine cerebral malaria development is independent of toll-like receptor signaling. Am J Pathol 170:1640–1648PubMedGoogle Scholar
  100. Togbe D, de Sousa PL, Fauconnier M, Boissay V, Fick L et al (2008) Both functional LTbeta receptor and TNF receptor 2 are required for the development of experimental cerebral malaria. PLoS One 3:e2608PubMedGoogle Scholar
  101. Tournamille C, Colin Y, Cartron JP, Le Van Kim C (1995) Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy-negative individuals. Nat Genet 10:224–228PubMedGoogle Scholar
  102. van den Steen PE, Deroost K, Van Aelst I, Geurts N, Martens E et al (2008) CXCR3 determines strain susceptibility to murine cerebral malaria by mediating T lymphocyte migration toward IFN-gamma-induced chemokines. Eur J Immunol 38:1082–1095PubMedGoogle Scholar
  103. van der Heyde HC, Pepper B, Batchelder J, Cigel F, Weidanz WP (1997) The time course of selected malarial infections in cytokine-deficient mice. Exp Parasitol 85:206–213PubMedGoogle Scholar
  104. van der Heyde HC, Nolan J, Combes V, Gramaglia I, Grau GE (2006) A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction. Trends Parasitol 22:503–508PubMedGoogle Scholar
  105. Verra F, Mangano VD, Modiano D (2009) Genetics of susceptibility to Plasmodium falciparum: from classical malaria resistance genes towards genome-wide association studies. Parasite Immunol 31:234–253PubMedGoogle Scholar
  106. Weatherall DJ, Miller LH, Baruch DI, Marsh K, Doumbo OK et al (2002) Malaria and the red cell. Hematology Am Soc Hematol Educ Program 2002:35–57Google Scholar
  107. White NJ, Turner GD, Medana IM, Dondorp AM, Day NP (2010) The murine cerebral malaria phenomenon. Trends Parasitol 26:11–15PubMedGoogle Scholar
  108. Williams TN, Maitland K, Bennett S, Ganczakowski M, Peto TE et al (1996) High incidence of malaria in alpha-thalassaemic children. Nature 383:522–525PubMedGoogle Scholar
  109. Wunderlich F, Mossmann H, Helwig M, Schillinger G (1988) Resistance to Plasmodium chabaudi in B10 mice: influence of the H-2 complex and testosterone. Infect Immun 56:2400–2406PubMedGoogle Scholar
  110. Yanez DM, Manning DD, Cooley AJ, Weidanz WP, van der Heyde HC (1996) Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria. J Immunol 157:1620–1624PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Rhea Longley
    • 1
  • Clare Smith
    • 1
  • Anny Fortin
    • 2
  • Joanne Berghout
    • 2
  • Brendan McMorran
    • 1
  • Gaétan Burgio
    • 1
  • Simon Foote
    • 1
    Email author
  • Philippe Gros
    • 2
  1. 1.Menzies Research InstituteUniversity of TasmaniaHobartAustralia
  2. 2.Department of BiochemistryMcGill UniversityMontrealCanada

Personalised recommendations