Advertisement

Seminars in Immunopathology

, Volume 34, Issue 6, pp 863–871 | Cite as

Th2 responses in schistosomiasis

  • Keke Fairfax
  • Marcia Nascimento
  • Stanley Ching-Cheng Huang
  • Bart Everts
  • Edward J. PearceEmail author
Review

Abstract

Schistosomiasis is caused by infection with parasitic flatworms of the genus Schistosoma. It is characterized by the development of strong CD4+ T cell and B cell responses that, during primary infection, fail to eliminate the parasites, but in collaboration with cells of the innate immune system allow survival in the face of ongoing tissue damage caused by the lodging of parasite eggs in the liver and the passage of eggs across the intestinal epithelium. Mounting a tightly controlled Th2 response is key to this outcome, and while this type of response is a risk factor for the development of fibrosis, it also underpins the development of resistance to further infection; as such, understanding how Th2 responses are induced and regulated in schistosomiasis remains a critical area of research.

Keywords

Helminth Parasite Th2 Fibrosis Macrophage Treg Tfh Eosinophil Immunopathology 

Notes

Acknowledgment

Work in the Pearce laboratory is supported by the NIH (to EJP) and by Merck-UNCF to KF.

References

  1. 1.
    Abdulla MH, Lim KC, McKerrow JH, Caffrey CR (2011) Proteomic identification of IPSE/alpha-1 as a major hepatotoxin secreted by Schistosoma mansoni eggs. PLoS Negl Trop Dis 5:e1368PubMedCrossRefGoogle Scholar
  2. 2.
    Amiri P, Locksley RM, Parslow TG et al (1992) Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature 356:604–607PubMedCrossRefGoogle Scholar
  3. 3.
    Amu S, Saunders SP, Kronenberg M, Mangan NE, Atzberger A, Fallon PG (2010) Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model. J Allergy Clin Immunol 125:1114–1124.e8PubMedCrossRefGoogle Scholar
  4. 4.
    Barron L, Wynn TA (2011) Macrophage activation governs schistosomiasis-induced inflammation and fibrosis. Eur J Immunol 41:2509–2514PubMedCrossRefGoogle Scholar
  5. 5.
    Baumgart M, Tompkins F, Leng J, Hesse M (2006) Naturally occurring CD4+Foxp3+ regulatory T cells are an essential, IL-10-independent part of the immunoregulatory network in Schistosoma mansoni egg-induced inflammation. J Immunol 176:5374–5387PubMedGoogle Scholar
  6. 6.
    Black CL, Mwinzi PN, Muok EM et al (2010) Influence of exposure history on the immunology and development of resistance to human schistosomiasis mansoni. PLoS Negl Trop Dis 4:e637PubMedCrossRefGoogle Scholar
  7. 7.
    Bosshardt SC, Freeman GL Jr, Secor WE, Colley DG (1997) IL-10 deficit correlates with chronic, hypersplenomegaly syndrome in male CBA/J mice infected with Schistosoma mansoni. Parasite Immunol 19:347–353PubMedCrossRefGoogle Scholar
  8. 8.
    Brunet LR, Finkelman FD, Cheever AW, Kopf MA, Pearce EJ (1997) IL-4 protects against TNF-alpha-mediated cachexia and death during acute schistosomiasis. J Immunol 159:777–785PubMedGoogle Scholar
  9. 9.
    Brunet LR, Kopf MA, Pearce EJ (1999) Schistosoma mansoni: IL-4 is necessary for concomitant immunity in mice. J Parasitol 85:734–736PubMedCrossRefGoogle Scholar
  10. 10.
    Buchanan RD, Fine DP, Colley DG (1973) Schistosoma mansoni infection in mice depleted of thymus-dependent lymphocytes. II. Pathology and altered pathogenesis. Am J Pathol 71:207–218PubMedGoogle Scholar
  11. 11.
    Byram JE, Doenhoff MJ, Musallam R, Brink LH, von Lichtenberg F (1979) Schistosoma mansoni infections in T-cell deprived mice, and the ameliorating effect of administering homologous chronic infection serum. II. Pathology. Am J Trop Med Hyg 28:274–285PubMedGoogle Scholar
  12. 12.
    Cardoso LS, Oliveira SC, Araujo MI (2012) Schistosoma mansoni antigens as modulators of the allergic inflammatory response in asthma. Endocrinol Metab Immune Disord Drug Targets 12:24–32CrossRefGoogle Scholar
  13. 13.
    Caserta S, Nausch N, Sawtell A et al (2012) Chronic infection drives expression of the inhibitory receptor CD200R, and its ligand CD200, by mouse and human CD4 T cells. PLoS One 7:e35466PubMedCrossRefGoogle Scholar
  14. 14.
    Colley DG, Sasser LE, Reed AM (2005) PD-L2+ dendritic cells and PD-1+ CD4+ T cells in schistosomiasis correlate with morbidity. Parasite Immunol 27:45–53PubMedCrossRefGoogle Scholar
  15. 15.
    Constant S, Pfeiffer C, Woodard A, Pasqualini T, Bottomly K (1995) Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells. J Exp Med 182:1591–1596PubMedCrossRefGoogle Scholar
  16. 16.
    Cooke A, Tonks P, Jones FM et al (1999) Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol 21:169–176PubMedCrossRefGoogle Scholar
  17. 17.
    de Oliveira Fraga LA, Torrero MN, Tocheva AS, Mitre E, Davies SJ (2010) Induction of type 2 responses by schistosome worms during prepatent infection. J Infect Dis 201:464–472PubMedCrossRefGoogle Scholar
  18. 18.
    Dewals BG, Marillier RG, Hoving JC, Leeto M, Schwegmann A, Brombacher F (2010) IL-4Ralpha-independent expression of mannose receptor and Ym1 by macrophages depends on their IL-10 responsiveness. PLoS Negl Trop Dis 4:e689PubMedCrossRefGoogle Scholar
  19. 19.
    Doenhoff M, Musallam R, Bain J, McGregor A (1979) Schistosoma mansoni infections in T-cell deprived mice, and the ameliorating effect of administering homologous chronic infection serum. I. Pathogenesis. Am J Trop Med Hyg 28:260–263PubMedGoogle Scholar
  20. 20.
    Doenhoff MJ, Pearson S, Dunne DW et al (1981) Immunological control of hepatotoxicity and parasite egg excretion in Schistosoma mansoni infections: stage specificity of the reactivity of immune serum in T-cell deprived mice. Trans R Soc Trop Med Hyg 75:41–53PubMedCrossRefGoogle Scholar
  21. 21.
    Donnelly S, O’Neill SM, Stack CM et al (2010) Helminth cysteine proteases inhibit TRIF-dependent activation of macrophages via degradation of TLR3. J Biol Chem 285:3383–3392PubMedCrossRefGoogle Scholar
  22. 22.
    Donnelly S, Stack CM, O’Neill SM, Sayed AA, Williams DL, Dalton JP (2008) Helminth 2-Cys peroxiredoxin drives Th2 responses through a mechanism involving alternatively activated macrophages. FASEB J 22:4022–4032PubMedCrossRefGoogle Scholar
  23. 23.
    Dunne DW, Butterworth AE, Fulford AJ et al (1992) Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection. Eur J Immunol 22:1483–1494PubMedCrossRefGoogle Scholar
  24. 24.
    Everts B, Hussaarts L, Driessen L et al (2012) Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor. J Exp Med 209:1753–1767PubMedCrossRefGoogle Scholar
  25. 25.
    Everts B, Perona-Wright G, Smits HH et al (2009) Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses. J Exp Med 206:1673–1680PubMedCrossRefGoogle Scholar
  26. 26.
    Everts B, Smits HH, Hokke CH, Yazdanbakhsh M (2010) Helminths and dendritic cells: sensing and regulating via pattern recognition receptors, Th2 and Treg responses. Eur J Immunol 40:1525–1537PubMedCrossRefGoogle Scholar
  27. 27.
    Fairfax KC, Amiel E, King IL, Freitas TC, Mohrs M, Pearce EJ (2012) IL-10R blockade during chronic schistosomiasis mansoni results in the loss of B cells from the liver and the development of severe pulmonary disease. PLoS Pathog 8:e1002490PubMedCrossRefGoogle Scholar
  28. 28.
    Fallon PG, Richardson EJ, McKenzie GJ, McKenzie AN (2000) Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent. J Immunol 164:2585–2591PubMedGoogle Scholar
  29. 29.
    Faveeuw C, Mallevaey T, Paschinger K et al (2003) Schistosome N-glycans containing core alpha 3-fucose and core beta 2-xylose epitopes are strong inducers of Th2 responses in mice. Eur J Immunol 33:1271–1281PubMedCrossRefGoogle Scholar
  30. 30.
    Fitzsimmons CM, Jones FM, Stearn A et al (2012) The Schistosoma mansoni tegumental-allergen-like (TAL) protein family: influence of developmental expression on human IgE responses. PLoS Negl Trop Dis 6:e1593PubMedCrossRefGoogle Scholar
  31. 31.
    Fitzsimmons CM, Schramm G, Jones FM et al (2005) Molecular characterization of omega-1: a hepatotoxic ribonuclease from Schistosoma mansoni eggs. Mol Biochem Parasitol 144:123–127PubMedCrossRefGoogle Scholar
  32. 32.
    Grant AV, Araujo MI, Ponte EV et al (2011) Polymorphisms in IL10 are associated with total Immunoglobulin E levels and Schistosoma mansoni infection intensity in a Brazilian population. Genes Immun 12:46–50PubMedCrossRefGoogle Scholar
  33. 33.
    Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Geijtenbeek TB (2009) Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori. Nat Immunol 10:1081–1088PubMedCrossRefGoogle Scholar
  34. 34.
    Grzych JM, Pearce E, Cheever A et al (1991) Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni. J Immunol 146:1322–1327PubMedGoogle Scholar
  35. 35.
    Herbert DR, Holscher C, Mohrs M et al (2004) Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity 20:623–635PubMedCrossRefGoogle Scholar
  36. 36.
    Herbert DR, Orekov T, Perkins C, Finkelman FD (2008) IL-10 and TGF-beta redundantly protect against severe liver injury and mortality during acute schistosomiasis. J Immunol 181:7214–7220PubMedGoogle Scholar
  37. 37.
    Herbert DR, Orekov T, Perkins C, Rothenberg ME, Finkelman FD (2008) IL-4R alpha expression by bone marrow-derived cells is necessary and sufficient for host protection against acute schistosomiasis. J Immunol 180:4948–4955PubMedGoogle Scholar
  38. 38.
    Herbert DR, Orekov T, Roloson A et al (2010) Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis. J Immunol 184:6438–6446PubMedCrossRefGoogle Scholar
  39. 39.
    Hernandez HJ, Wang Y, Tzellas N, Stadecker MJ (1997) Expression of class II, but not class I, major histocompatibility complex molecules is required for granuloma formation in infection with Schistosoma mansoni. Eur J Immunol 27:1170–1176PubMedCrossRefGoogle Scholar
  40. 40.
    Hoffmann KF, Cheever AW, Wynn TA (2000) IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J Immunol 164:6406–6416PubMedGoogle Scholar
  41. 41.
    Hu JS, Freeman CM, Stolberg VR et al (2006) AMD3465, a novel CXCR4 receptor antagonist, abrogates schistosomal antigen-elicited (type-2) pulmonary granuloma formation. Am J Pathol 169:424–432PubMedCrossRefGoogle Scholar
  42. 42.
    Huber S, Hoffmann R, Muskens F, Voehringer D (2010) Alternatively activated macrophages inhibit T-cell proliferation by Stat6-dependent expression of PD-L2. Blood 116:3311–3320PubMedCrossRefGoogle Scholar
  43. 43.
    Jakubzick C, Wen H, Matsukawa A, Keller M, Kunkel SL, Hogaboam CM (2004) Role of CCR4 ligands, CCL17 and CCL22, during Schistosoma mansoni egg-induced pulmonary granuloma formation in mice. Am J Pathol 165:1211–1221PubMedCrossRefGoogle Scholar
  44. 44.
    Jankovic D, Cheever AW, Kullberg MC et al (1998) CD4+ T cell-mediated granulomatous pathology in schistosomiasis is downregulated by a B cell-dependent mechanism requiring Fc receptor signaling. J Exp Med 187:619–629PubMedCrossRefGoogle Scholar
  45. 45.
    Joseph S, Jones FM, Walter K et al (2004) Increases in human T helper 2 cytokine responses to Schistosoma mansoni worm and worm-tegument antigens are induced by treatment with praziquantel. J Infect Dis 190:835–842PubMedCrossRefGoogle Scholar
  46. 46.
    Joyce KL, Morgan W, Greenberg R, Nair MG (2012) Using eggs from Schistosoma mansoni as an in vivo model of helminth-induced lung inflammation. J Vis Exp 64:e3905PubMedGoogle Scholar
  47. 47.
    Kabatereine NB, Vennervald BJ, Ouma JH et al (1999) Adult resistance to schistosomiasis mansoni: age-dependence of reinfection remains constant in communities with diverse exposure patterns. Parasitology 118(Pt 1):101–105PubMedCrossRefGoogle Scholar
  48. 48.
    Karanja DM, Hightower AW, Colley DG et al (2002) Resistance to reinfection with Schistosoma mansoni in occupationally exposed adults and effect of HIV-1 co-infection on susceptibility to schistosomiasis: a longitudinal study. Lancet 360:592–596PubMedCrossRefGoogle Scholar
  49. 49.
    King CH, Dickman K, Tisch DJ (2005) Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet 365:1561–1569PubMedCrossRefGoogle Scholar
  50. 50.
    La Flamme AC, Patton EA, Bauman B, Pearce EJ (2001) IL-4 plays a crucial role in regulating oxidative damage in the liver during schistosomiasis. J Immunol 166:1903–1911PubMedGoogle Scholar
  51. 51.
    La Flamme AC, Ruddenklau K, Backstrom BT (2003) Schistosomiasis decreases central nervous system inflammation and alters the progression of experimental autoimmune encephalomyelitis. Infect Immun 71:4996–5004PubMedCrossRefGoogle Scholar
  52. 52.
    Larson D, Hubner MP, Torrero MN et al (2012) Chronic helminth infection reduces basophil responsiveness in an IL-10-dependent manner. J Immunol 188:4188–4199PubMedCrossRefGoogle Scholar
  53. 53.
    Layland LE, Rad R, Wagner H, da Costa CU (2007) Immunopathology in schistosomiasis is controlled by antigen-specific regulatory T cells primed in the presence of TLR2. Eur J Immunol 37:2174–2184PubMedCrossRefGoogle Scholar
  54. 54.
    Leptak CL, McKerrow JH (1997) Schistosome egg granulomas and hepatic expression of TNF-alpha are dependent on immune priming during parasite maturation. J Immunol 158:301–307PubMedGoogle Scholar
  55. 55.
    MacDonald AS, Straw AD, Bauman B, Pearce EJ (2001) CD8- dendritic cell activation status plays an integral role in influencing Th2 response development. J Immunol 167:1982–1988PubMedGoogle Scholar
  56. 56.
    MacDonald AS, Patton EA, La Flamme AC et al (2002) Impaired Th2 development and increased mortality during Schistosoma mansoni infection in the absence of CD40/CD154 interaction. J Immunol 168:4643–4649PubMedGoogle Scholar
  57. 57.
    MacDonald AS, Straw AD, Dalton NM, Pearce EJ (2002) Cutting edge: Th2 response induction by dendritic cells: a role for CD40. J Immunol 168:537–540PubMedGoogle Scholar
  58. 58.
    Madala SK, Pesce JT, Ramalingam TR et al (2010) Matrix metalloproteinase 12-deficiency augments extracellular matrix degrading metalloproteinases and attenuates IL-13-dependent fibrosis. J Immunol 184:3955–3963PubMedCrossRefGoogle Scholar
  59. 59.
    Mathew RC, Boros DL (1986) Anti-L3T4 antibody treatment suppresses hepatic granuloma formation and abrogates antigen-induced interleukin-2 production in Schistosoma mansoni infection. Infect Immun 54:820–826PubMedGoogle Scholar
  60. 60.
    McKee AS, Pearce EJ (2004) CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development. J Immunol 173:1224–1231PubMedGoogle Scholar
  61. 61.
    Murray PJ, Wynn TA (2011) Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 11:723–737PubMedCrossRefGoogle Scholar
  62. 62.
    Nair MG, Du Y, Perrigoue JG et al (2009) Alternatively activated macrophage-derived RELM-{alpha} is a negative regulator of type 2 inflammation in the lung. J Exp Med 206:937–952PubMedCrossRefGoogle Scholar
  63. 63.
    Okano M, Satoskar AR, Nishizaki K, Abe M, Harn DA Jr (1999) Induction of Th2 responses and IgE is largely due to carbohydrates functioning as adjuvants on Schistosoma mansoni egg antigens. J Immunol 163:6712–6717PubMedGoogle Scholar
  64. 64.
    Okano M, Satoskar AR, Nishizaki K, Harn DA Jr (2001) Lacto-N-fucopentaose III found on Schistosoma mansoni egg antigens functions as adjuvant for proteins by inducing Th2-type response. J Immunol 167:442–450PubMedGoogle Scholar
  65. 65.
    Paveley RA, Aynsley SA, Turner JD et al (2011) The mannose receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNgamma production. Int J Parasitol 41:1335–1345PubMedCrossRefGoogle Scholar
  66. 66.
    Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A (1991) Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med 173:159–166PubMedCrossRefGoogle Scholar
  67. 67.
    Pearce EJ, MacDonald AS (2002) The immunobiology of schistosomiasis. Nat Rev Immunol 2:499–511PubMedCrossRefGoogle Scholar
  68. 68.
    Perrigoue JG, Saenz SA, Siracusa MC et al (2009) MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity. Nat Immunol 10:697–705PubMedCrossRefGoogle Scholar
  69. 69.
    Pesce JT, Ramalingam TR, Mentink-Kane MM et al (2009) Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog 5:e1000371PubMedCrossRefGoogle Scholar
  70. 70.
    Pesce JT, Ramalingam TR, Wilson MS et al (2009) Retnla (relmalpha/fizz1) suppresses helminth-induced Th2-type immunity. PLoS Pathog 5:e1000393PubMedCrossRefGoogle Scholar
  71. 71.
    Phillips SM, Colley DG (1978) Immunologic aspects of host responses to schistosomiasis: resistance, immunopathology, and eosinophil involvement. Prog Allergy 24:49–182PubMedGoogle Scholar
  72. 72.
    Phythian-Adams AT, Cook PC, Lundie RJ et al (2011) CD11c depletion severely disrupts Th2 induction and development in vivo. J Exp Med 207:2089–2096CrossRefGoogle Scholar
  73. 73.
    Ramalingam TR, Pesce JT, Mentink-Kane MM et al (2009) Regulation of helminth-induced Th2 responses by thymic stromal lymphopoietin. J Immunol 182:6452–6459PubMedCrossRefGoogle Scholar
  74. 74.
    Ritter M, Gross O, Kays S et al (2010) Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses. Proc Natl Acad Sci U S A 107:20459–20464PubMedCrossRefGoogle Scholar
  75. 75.
    Rutitzky LI, Stadecker MJ (2011) Exacerbated egg-induced immunopathology in murine Schistosoma mansoni infection is primarily mediated by IL-17 and restrained by IFN-gamma. Eur J Immunol 41:2677–2687PubMedCrossRefGoogle Scholar
  76. 76.
    Sadler CH, Rutitzky LI, Stadecker MJ, Wilson RA (2003) IL-10 is crucial for the transition from acute to chronic disease state during infection of mice with Schistosoma mansoni. Eur J Immunol 33:880–888PubMedCrossRefGoogle Scholar
  77. 77.
    Schramm G, Gronow A, Knobloch J et al (2006) IPSE/alpha-1: a major immunogenic component secreted from Schistosoma mansoni eggs. Mol Biochem Parasitol 147:9–19PubMedCrossRefGoogle Scholar
  78. 78.
    Schramm G, Mohrs K, Wodrich M et al (2007) Cutting edge: IPSE/alpha-1, a glycoprotein from Schistosoma mansoni eggs, induces IgE-dependent, antigen-independent IL-4 production by murine basophils in vivo. J Immunol 178:6023–6027PubMedGoogle Scholar
  79. 79.
    Shainheit MG, Lasocki KW, Finger E et al (2011) The pathogenic Th17 cell response to major schistosome egg antigen is sequentially dependent on IL-23 and IL-1beta. J Immunol 187:5328–5335PubMedCrossRefGoogle Scholar
  80. 80.
    Sher A, Coffman RL, Hieny S, Scott P, Cheever AW (1990) Interleukin 5 is required for the blood and tissue eosinophilia but not granuloma formation induced by infection with Schistosoma mansoni. Proc Natl Acad Sci U S A 87:61–65PubMedCrossRefGoogle Scholar
  81. 81.
    Siracusa MC, Comeau MR, Artis D (2011) New insights into basophil biology: initiators, regulators, and effectors of type 2 inflammation. Ann N Y Acad Sci 1217:166–177PubMedCrossRefGoogle Scholar
  82. 82.
    Smith P, Mangan NE, Walsh CM et al (2007) Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism. J Immunol 178:4557–4566PubMedGoogle Scholar
  83. 83.
    Smith P, Walsh CM, Mangan NE et al (2004) Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages. J Immunol 173:1240–1248PubMedGoogle Scholar
  84. 84.
    Steinfelder S, Andersen JF, Cannons JL et al (2009) The major component in schistosome eggs responsible for conditioning dendritic cells for Th2 polarization is a T2 ribonuclease (omega-1). J Exp Med 206:1681–1690PubMedCrossRefGoogle Scholar
  85. 85.
    Sullivan BM, Liang HE, Bando JK et al (2011) Genetic analysis of basophil function in vivo. Nat Immunol 12:527–535PubMedCrossRefGoogle Scholar
  86. 86.
    Taylor JJ, Krawczyk CM, Mohrs M, Pearce EJ (2009) Th2 cell hyporesponsiveness during chronic murine schistosomiasis is cell intrinsic and linked to GRAIL expression. J Clin Invest 119:1019–1028PubMedCrossRefGoogle Scholar
  87. 87.
    Taylor JJ, Mohrs M, Pearce EJ (2006) Regulatory T cell responses develop in parallel to Th responses and control the magnitude and phenotype of the Th effector population. J Immunol 176:5839–5847PubMedGoogle Scholar
  88. 88.
    Turner JD, Jenkins GR, Hogg KG et al (2011) CD4+CD25+ regulatory cells contribute to the regulation of colonic Th2 granulomatous pathology caused by schistosome infection. PLoS Negl Trop Dis 5:e1269PubMedCrossRefGoogle Scholar
  89. 89.
    Van de Vijver KK, Deelder AM, Jacobs W, Van Marck EA, Hokke CH (2006) LacdiNAc- and LacNAc-containing glycans induce granulomas in an in vivo model for schistosome egg-induced hepatic granuloma formation. Glycobiology 16:237–243PubMedCrossRefGoogle Scholar
  90. 90.
    van der Vlugt LE, Labuda LA, Ozir-Fazalalikhan A et al (2012) Schistosomes induce regulatory features in human and mouse CD1d(hi) B cells: inhibition of allergic inflammation by IL-10 and regulatory T cells. PLoS One 7:e30883PubMedCrossRefGoogle Scholar
  91. 91.
    van Die I, van Vliet SJ, Nyame AK et al (2003) The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x. Glycobiology 13:471–478PubMedCrossRefGoogle Scholar
  92. 92.
    Watanabe K, Carter JM, Neely-Burnam M, Colley DG (2009) Relative imbalance between T regulatory cells and activated T cells in mice with differential morbidity in chronic Schistosoma mansoni infections. Parasite Immunol 31:440–446PubMedCrossRefGoogle Scholar
  93. 93.
    Wherry EJ (2011) T cell exhaustion. Nat Immunol 12:492–499PubMedCrossRefGoogle Scholar
  94. 94.
    Wilson MS, Mentink-Kane MM, Pesce JT, Ramalingam TR, Thompson R, Wynn TA (2007) Immunopathology of schistosomiasis. Immunol Cell Biol 85:148–154PubMedCrossRefGoogle Scholar
  95. 95.
    Wilson S, Vennervald BJ, Kadzo H et al (2007) Hepatosplenomegaly in Kenyan schoolchildren: exacerbation by concurrent chronic exposure to malaria and Schistosoma mansoni infection. Trop Med Int Health 12:1442–1449PubMedCrossRefGoogle Scholar
  96. 96.
    Wilson S, Jones FM, Mwatha JK et al (2008) Hepatosplenomegaly is associated with low regulatory and Th2 responses to schistosome antigens in childhood schistosomiasis and malaria coinfection. Infect Immun 76:2212–2218PubMedCrossRefGoogle Scholar
  97. 97.
    Wilson S, Jones FM, Mwatha JK et al (2009) Hepatosplenomegaly associated with chronic malaria exposure: evidence for a pro-inflammatory mechanism exacerbated by schistosomiasis. Parasite Immunol 31:64–71PubMedCrossRefGoogle Scholar
  98. 98.
    Wilson MS, Cheever AW, White SD, Thompson RW, Wynn TA (2011) IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni. PLoS Pathog 7:e1002171PubMedCrossRefGoogle Scholar
  99. 99.
    Wilson S, Vennervald BJ, Dunne DW (2011) Chronic hepatosplenomegaly in African school children: a common but neglected morbidity associated with schistosomiasis and malaria. PLoS Negl Trop Dis 5:e1149PubMedCrossRefGoogle Scholar
  100. 100.
    Woolhouse ME, Hagan P (1999) Seeking the ghost of worms past. Nat Med 5:1225–1227PubMedCrossRefGoogle Scholar
  101. 101.
    Wynn TA, Cheever AW, Williams ME et al (1998) IL-10 regulates liver pathology in acute murine schistosomiasis mansoni but is not required for immune down-modulation of chronic disease. J Immunol 160:4473–4480PubMedGoogle Scholar
  102. 102.
    Wynn TA, Thompson RW, Cheever AW, Mentink-Kane MM (2004) Immunopathogenesis of schistosomiasis. Immunol Rev 201:156–167PubMedCrossRefGoogle Scholar
  103. 103.
    Zaccone P, Burton O, Miller N, Jones FM, Dunne DW, Cooke A (2009) Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice. Eur J Immunol 39:1098–1107PubMedCrossRefGoogle Scholar
  104. 104.
    Zaccone P, Burton OT, Gibbs SE et al (2011) The S. mansoni glycoprotein omega-1 induces Foxp3 expression in NOD mouse CD4(+) T cells. Eur J Immunol 41:2709–2718PubMedCrossRefGoogle Scholar
  105. 105.
    Zaccone P, Fehervari Z, Jones FM et al (2003) Schistosoma mansoni antigens modulate the activity of the innate immune response and prevent onset of type 1 diabetes. Eur J Immunol 33:1439–1449PubMedCrossRefGoogle Scholar
  106. 106.
    Zaretsky AG, Taylor JJ, King IL, Marshall FA, Mohrs M, Pearce EJ (2009) T follicular helper cells differentiate from Th2 cells in response to helminth antigens. J Exp Med 206:991–999PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Keke Fairfax
    • 1
  • Marcia Nascimento
    • 1
  • Stanley Ching-Cheng Huang
    • 1
  • Bart Everts
    • 1
  • Edward J. Pearce
    • 1
    • 2
    Email author
  1. 1.Division of Immunobiology, Department of Pathology and ImmunologyWashington University School of MedicineSt. LouisUSA
  2. 2.St. LouisUSA

Personalised recommendations