The immunobiology of schistosomiasis (original) (raw)
van der Werf, M. J. et al. Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta Tropica (in the press).A comprehensive assessment of the true impact of schistosomiasis on human health.
Dunne, D. W. & Pearce, E. J. Immunology of hepatosplenic schistosomiasis mansoni: a human perspective. Microbes Infect.1, 553–560 (1999). CASPubMed Google Scholar
Cheever, A. W., Hoffmann, K. F. & Wynn, T. A. Immunopathology of schistosomiasis mansoni in mice and men. Immunol. Today21, 465–466 (2000). CASPubMed Google Scholar
Rabello, A. Acute human schistosomiasis mansoni. Mem. Inst. Oswaldo Cruz90, 277–280 (1995). CASPubMed Google Scholar
de Jesus, A. R. et al. Clinical and immunologic evaluation of 31 patients with acute schistosomiasis mansoni. J. Infect. Dis.185, 98–105 (2002). PubMed Google Scholar
Montenegro, S. M. et al. Cytokine production in acute versus chronic human schistosomiasis mansoni: the cross-regulatory role of interferon-γ and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens. J. Infect. Dis.179, 1502–1514 (1999). CASPubMed Google Scholar
King, C. L. et al. B-cell sensitization to helminthic infection develops in utero in humans. J. Immunol.160, 3578–3584 (1998). CASPubMed Google Scholar
Malhotra, I. et al. In utero exposure to helminth and mycobacterial antigens generates cytokine responses similar to that observed in adults. J. Clin. Invest.99, 1759–1766 (1997). CASPubMedPubMed Central Google Scholar
Brunet, L. R., Finkelman, F. D., Cheever, A. W., Kopf, M. A. & Pearce, E. J. IL-4 protects against TNF-α-mediated cachexia and death during acute schistosomiasis. J. Immunol.159, 777–785 (1997).The first paper to show that the TH2 response that is induced during schistosomiasis is essential for host survival. CASPubMed Google Scholar
Fallon, P. G., Richardson, E. J., McKenzie, G. J. & McKenzie, A. N. 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, 2585–2591 (2000). CASPubMed Google Scholar
La Flamme, A. C., Patton, E. A., Bauman, B. & Pearce, E. J. IL-4 plays a crucial role in regulating oxidative damage in the liver during schistosomiasis. J. Immunol.166, 1903–1911 (2001). CASPubMed Google Scholar
Hatz, C. F. The use of ultrasound in schistosomiasis. Adv. Parasitol.48, 225–284 (2001). CASPubMed Google Scholar
Jankovic, D. et al. Schistosome-infected IL-4 receptor knockout (KO) mice, in contrast to IL-4 KO mice, fail to develop granulomatous pathology while maintaining the same lymphokine expression profile. J. Immunol.163, 337–342 (1999). CASPubMed Google Scholar
Chiaramonte, M. G., Donaldson, D. D., Cheever, A. W. & Wynn, T. A. An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type-2-dominated inflammatory response. J. Clin. Invest.104, 777–785 (1999).This report established IL-13 as a profibrogenic mediator in schistosomiasis, and it describes a rationally designed experimental immunotherapy that blocks fibrosis. CASPubMedPubMed Central Google Scholar
Modolell, M., Corraliza, I. M., Link, F., Soler, G. & Eichmann, K. Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone-marrow-derived macrophages by TH1 and TH2 cytokines. Eur. J. Immunol.25, 1101–1104 (1995). CASPubMed Google Scholar
Hesse, M., Cheever, A. W., Jankovic, D. & Wynn, T. A. NOS-2 mediates the protective anti-inflammatory and antifibrotic effects of the TH1-inducing adjuvant, IL-12, in a TH2 model of granulomatous disease. Am. J. Pathol.157, 945–955 (2000). CASPubMedPubMed Central Google Scholar
Lee, C. G. et al. Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor-β1. J. Exp. Med.194, 809–821 (2001). CASPubMedPubMed Central Google Scholar
Hesse, M. et al. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of l-arginine metabolism. J. Immunol.167, 6533–6544 (2001). CASPubMed Google Scholar
Mohamed-Ali, Q. et al. Susceptibility to periportal (Symmers) fibrosis in human Schistosoma mansoni infections: evidence that intensity and duration of infection, gender and inherited factors are critical in disease progression. J. Infect. Dis.180, 1298–1306 (1999). CASPubMed Google Scholar
Dessein, A. J. et al. Severe hepatic fibrosis in Schistosoma mansoni infection is controlled by a major locus that is closely linked to the interferon-γ receptor gene. Am. J. Hum. Genet.65, 709–721 (1999).Severe schistosomiasis occurs in less than 10% of infected individuals. This report is an important step towards understanding the genetic predispostion to severe disease. CASPubMedPubMed Central Google Scholar
Araujo, M. I. et al. Evidence of a T helper type-2 activation in human schistosomiasis. Eur. J. Immunol.26, 1399–1403 (1996). CASPubMed Google Scholar
Williams, M. E. et al. Leukocytes of patients with Schistosoma mansoni respond with a TH2 pattern of cytokine production to mitogen or egg antigens, but with a TH0 pattern to worm antigens. J. Infect. Dis.170, 946–954 (1994). CASPubMed Google Scholar
Mwatha, J. K. et al. High levels of TNF, soluble TNF receptors, soluble ICAM-1, and IFN-γ, but low levels of IL-5, are associated with hepatosplenic disease in human schistosomiasis mansoni. J. Immunol.160, 1992–1999 (1998). CASPubMed Google Scholar
Dessein, A. J. et al. Infection and disease in human schistosomiasis mansoni are under distinct major gene control. Microbes Infect.1, 561–567 (1999). CASPubMed Google Scholar
Montesano, M. A., Colley, D. G., Willard, M. T., Freeman, G. L. Jr & Secor, W. E. Idiotypes expressed early in experimental Schistosoma mansoni infections predict clinical outcomes of chronic disease. J. Exp. Med.195, 1223–1228 (2002). CASPubMedPubMed Central Google Scholar
Bosshardt, S. C., Freeman, G. L. Jr, Secor, W. E. & Colley, D. G. IL-10 deficit correlates with chronic, hypersplenomegaly syndrome in male CBA/J mice infected with Schistosoma mansoni. Parasite Immunol.19, 347–353 (1997). CASPubMed Google Scholar
Montesano, M. A., Colley, D. G., Eloi-Santos, S., Freeman, G. L. Jr & Secor, W. E. Neonatal idiotypic exposure alters subsequent cytokine, pathology and survival patterns in experimental Schistosoma mansoni infections. J. Exp. Med.189, 637–645 (1999). CASPubMed Google Scholar
Hoffmann, K. F., Cheever, A. W. & Wynn, T. A. 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, 6406–6416 (2000).This study establishes the immunological requirements for minimizing disease during the acute and chronic phases of schistosomiasis. CASPubMed Google Scholar
Vaillant, B., Chiaramonte, M. G., Cheever, A. W., Soloway, P. D. & Wynn, T. A. Regulation of hepatic fibrosis and extracellular matrix genes by the TH response: new insight into the role of tissue inhibitors of matrix metalloproteinases. J. Immunol.167, 7017–7026 (2001). CASPubMed Google Scholar
King, C. L. et al. _Schistosoma haematobium_-induced urinary-tract morbidity correlates with increased tumor-necrosis factor-α and diminished interleukin-10 production. J. Infect. Dis.184, 1176–1182 (2001). CASPubMed Google Scholar
Colley, D. G. In Idiotypic Network and Diseases (eds Cerney, J. & Hiernauz, J.) 71–105 (American Society for Microbiology, Washington DC, 1990). Google Scholar
King, C. L. et al. Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity. J. Immunol.156, 4715–4721 (1996). CASPubMed Google Scholar
Wynn, T. A. et al. An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection. Nature376, 594–596 (1995). CASPubMed Google Scholar
Rutitzky, L. I., Hernandez, H. J. & Stadecker, M. J. TH1-polarizing immunization with egg antigens correlates with severe exacerbation of immunopathology and death in schistosome infection. Proc. Natl Acad. Sci. USA98, 13243–13248 (2001).References33and34show that induced TH1 responses against egg antigens can lead to reduced hepatic fibrosis, but that there is a risk of severe disease in mice that are immunologically polarized in this way. These papers emphasize the importance of the appropriate immunological balance for optimal outcome during infection. CASPubMedPubMed Central Google Scholar
Wynn, T. A., Eltoum, I., Oswald, I. P., Cheever, A. W. & Sher, A. Endogenous interleukin-12 (IL-12) regulates granuloma formation induced by eggs of Schistosoma mansoni, and exogenous IL-12 both inhibits and prophylactically immunizes against egg pathology. J. Exp. Med.179, 1551–1561 (1994). CASPubMed Google Scholar
Morris, S. C. et al. Effects of IL-12 on in vivo cytokine gene expression and Ig-isotype selection. J. Immunol.152, 1047–1056 (1994). CASPubMed Google Scholar
Hernandez, H. J., Wang, Y. & Stadecker, M. J. In infection with Schistosoma mansoni, B cells are required for T helper type-2 cell responses but not for granuloma formation. J. Immunol.158, 4832–4837 (1997). CASPubMed Google Scholar
Jankovic, D. et al. CD4+ T-cell-mediated granulomatous pathology in schistosomiasis is downregulated by a B-cell-dependent mechanism requiring Fc receptor signaling. J. Exp. Med.187, 619–629 (1998). CASPubMedPubMed Central Google Scholar
Hernandez, H. J., Sharpe, A. H. & Stadecker, M. J. Experimental murine schistosomiasis in the absence of B7 costimulatory molecules: reversal of elicited T-cell cytokine profile and partial inhibition of egg granuloma formation. J. Immunol.162, 2884–2889 (1999). CASPubMed Google Scholar
MacDonald, A. S. et al. Impaired TH2 development and increased mortality during Schistosoma mansoni infection in the absence of CD40/CD154 interaction. J. Immunol.168, 4643–4649 (2002). CASPubMed Google Scholar
Salzet, M., Capron, A. & Stefano, G. B. Molecular crosstalk in host–parasite relationships: schistosome– and leech–host interactions. Parasitol. Today16, 536–540 (2000). CASPubMed Google Scholar
Basch, P. F. & Rhine, W. D. Schistosoma mansoni: reproductive potential of male and female worms cultured in vitro. J. Parasitol.69, 567–569 (1983). CASPubMed Google Scholar
Amiri, P. et al. Tumour-necrosis factor-α restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature356, 604–607 (1992). CASPubMed Google Scholar
Harrison, R. A. & Doenhoff, M. J. Retarded development of Schistosoma mansoni in immunosuppressed mice. Parasitology86, 429–438 (1983). PubMed Google Scholar
Davies, S. J. et al. Modulation of blood-fluke development in the liver by hepatic CD4+ lymphocytes. Science294, 1358–1361 (2001).This study expands on previous reports that schistosomes fail to develop properly in hosts that lack T cells. It raises many unanswered questions about the role of the previously unidentified CD4+ subset of hepatic lymphocytes that seems to have an important role in this process, and the identity of the mediator they produce that is used by the parasites. CASPubMed Google Scholar
Wolowczuk, I. et al. Infection of mice lacking interleukin-7 (IL-7) reveals an unexpected role for IL-7 in the development of the parasite Schistosoma mansoni. Infect. Immun.67, 4183–4190 (1999). CASPubMedPubMed Central Google Scholar
Cheever, A. W., Poindexter, R. W. & Wynn, T. A. Egg laying is delayed but worm fecundity is normal in SCID mice infected with Schistosoma japonicum and S. mansoni with or without recombinant tumor-necrosis factor-α treatment. Infect. Immun.67, 2201–2208 (1999). CASPubMedPubMed Central Google Scholar
Davies, S. J. & McKerrow, J. H. In Biology of Parasitism (eds Tschudi, C. & Pearce, E. J.) 273–290 (Kluwer, Boston, 2001). Google Scholar
Beall, M. J. & Pearce, E. J. Human transforming growth factor-β activates a receptor serine/threonine kinase from the intravascular parasite Schistosoma mansoni. J. Biol. Chem.276, 31613–31619 (2001). CASPubMed Google Scholar
Murphy, K. M. T-lymphocyte differentiation in the periphery. Curr. Opin. Immunol.10, 226–232 (1998). CASPubMed Google Scholar
Ouyang, W. et al. Stat6-independent GATA-3 autoactivation directs IL-4-independent TH2 development and commitment. Immunity12, 27–37 (2000). CASPubMed Google Scholar
Ouyang, W. et al. Inhibition of TH1 development mediated by GATA-3 through an IL-4-independent mechanism. Immunity9, 745–755 (1998). CASPubMed Google Scholar
Sabin, E. A., Araujo, M. I., Carvalho, E. M. & Pearce, E. J. Impairment of tetanus toxoid-specific TH1-like immune responses in humans infected with Schistosoma mansoni. J. Infect. Dis.173, 269–272 (1996). CASPubMed Google Scholar
Malhotra, I. et al. Helminth- and Bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. J. Immunol.162, 6843–6848 (1999). CASPubMed Google Scholar
Kullberg, M. C., Pearce, E. J., Hieny, S. E., Sher, A. & Berzofsky, J. A. Infection with Schistosoma mansoni alters TH1/TH2 cytokine responses to a non-parasite antigen. J. Immunol.148, 3264–3270 (1992). CASPubMed Google Scholar
Cooper, P. J., Espinel, I., Paredes, W., Guderian, R. H. & Nutman, T. B. Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis: a possible role for interleukin-10. J. Infect. Dis.178, 1133–1138 (1998). CASPubMed Google Scholar
Actor, J. K. et al. Helminth infection results in decreased virus-specific CD8+ cytotoxic T-cell and TH1 cytokine responses, as well as delayed virus clearance. Proc. Natl Acad. Sci. USA90, 948–952 (1993). CASPubMedPubMed Central Google Scholar
Helmby, H., Kullberg, M. & Troye-Blomberg, M. Altered immune responses in mice with concomitant Schistosoma mansoni and Plasmodium chabaudi infections. Infect. Immun.66, 5167–5174 (1998). CASPubMedPubMed Central Google Scholar
Marshall, A. J. et al. Toxoplasma gondii and Schistosoma mansoni synergize to promote hepatocyte dysfunction associated with high levels of plasma TNF-α and early death in C57BL/6 mice. J. Immunol.163, 2089–2097 (1999). CASPubMed Google Scholar
Kamal, S. M. et al. Specific cellular immune response and cytokine patterns in patients coinfected with hepatitis C virus and Schistosoma mansoni. J. Infect. Dis.184, 972–982 (2001). CASPubMed Google Scholar
Kamal, S. M. et al. Acute hepatitis C without and with schistosomiasis: correlation with hepatitis-C-specific CD4+ T-cell and cytokine response. Gastroenterology121, 646–656 (2001). CASPubMed Google Scholar
McClary, H., Koch, R., Chisari, F. V. & Guidotti, L. G. Inhibition of hepatitis B virus replication during Schistosoma mansoni infection in transgenic mice. J. Exp. Med.192, 289–294 (2000). CASPubMedPubMed Central Google Scholar
Brunet, L. R., Beall, M., Dunne, D. W. & Pearce, E. J. Nitric oxide and the TH2 response combine to prevent severe hepatic damage during Schistosoma mansoni infection. J. Immunol.163, 4976–4984 (1999). CASPubMed Google Scholar
Frank, C. et al. The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet355, 887–891 (2000). CASPubMed Google Scholar
Maggi, E. et al. Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells. Science265, 244–248 (1994). CASPubMed Google Scholar
Bentwich, Z., Kalinkovich, A. & Weisman, Z. Immune activation is a dominant factor in the pathogenesis of African AIDS. Immunol. Today16, 187–191 (1995). CASPubMed Google Scholar
Bentwich, Z. et al. Can eradication of helminthic infections change the face of AIDS and tuberculosis? Immunol. Today20, 485–487 (1999). CASPubMed Google Scholar
Mwinzi, P. N., Karanja, D. M., Colley, D. G., Orago, A. S. & Secor, W. E. Cellular immune responses of schistosomiasis patients are altered by human immunodeficiency virus type 1 coinfection. J. Infect. Dis.184, 488–496 (2001). CASPubMed Google Scholar
Curry, A. J. et al. Evidence that cytokine-mediated immune interactions induced by Schistosoma mansoni alter disease outcome in mice concurrently infected with Trichuris muris. J. Exp. Med.181, 769–774 (1995). CASPubMed Google Scholar
Cooke, A. et al. Infection with Schistosoma mansoni prevents insulin-dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol.21, 169–176 (1999). CASPubMed Google Scholar
Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet351, 1225–1232 (1998).
Yazdanbakhsh, M., Kremsner, P. G. & van Ree, R. Allergy, parasites and the hygiene hypothesis. Science296, 490–494 (2002). CASPubMed Google Scholar
Wills-Karp, M., Santeli, J. & Karp, C. L. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nature Rev. Immunol.1, 69–74 (2001). CAS Google Scholar
Araujo, M. I. et al. Inverse association between skin response to aeroallergens and Schistosoma mansoni infection. Int. Arch. Allergy Immunol.123, 145–148 (2000). CASPubMed Google Scholar
van den Biggelaar, A. H. et al. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet356, 1723–1727 (2000).The identification of IL-10 as an important regulator of allergic manifestations in schistosomiasis. This area is reviewed in detail in reference72. CASPubMed Google Scholar
Butterworth, A. E. et al. Immunity and morbidity in human schistosomiasis mansoni. Trop. Geogr. Med.46, 197–208 (1994). CASPubMed Google Scholar
Dunne, D. W. et al. Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection. Eur. J. Immunol.22, 1483–1494 (1992). CASPubMed Google Scholar
Demeure, C. E. et al. Resistance to Schistosoma mansoni in humans: influence of the IgE/IgG4 balance and IgG2 in immunity to reinfection after chemotherapy. J. Infect. Dis.168, 1000–1008 (1993). CASPubMed Google Scholar
Rihet, P., Demeure, C. E., Bourgois, A., Prata, A. & Dessein, A. J. Evidence for an association between human resistance to Schistosoma mansoni and high anti-larval IgE levels. Eur. J. Immunol.21, 2679–2686 (1991). CASPubMed Google Scholar
Hagan, P., Blumenthal, U. J., Dunn, D., Simpson, A. J. & Wilkins, H. A. Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature349, 243–245 (1991). CASPubMed Google Scholar
Woolhouse, M. E. & Hagan, P. Seeking the ghost of worms past. Nature Med.5, 1225–1227 (1999). CASPubMed Google Scholar
Marquet, S. et al. Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31–q33. Nature Genet.14, 181–184 (1996). CASPubMed Google Scholar
Nutten, S. et al. From allergy to schistosomes: role of Fc receptors and adhesion molecules in eosinophil effector function. Mem. Inst. Oswaldo Cruz92 (Suppl. 2), 9–14 (1997). CASPubMed Google Scholar
Dombrowicz, D. & Capron, M. Eosinophils, allergy and parasites. Curr. Opin. Immunol.13, 716–720 (2001). CASPubMed Google Scholar
Wilson, R. A., Coulson, P. S. & McHugh, S. M. A significant part of the 'concomitant immunity' of mice to Schistosoma mansoni is the consequence of a leaky hepatic portal system, not immune killing. Parasite Immunol.5, 595–601 (1983). CASPubMed Google Scholar
Finkelman, F. D. & Urban, J. F. Jr. The other side of the coin: the protective role of the TH2 cytokines. J. Allergy Clin. Immunol.107, 772–780 (2001). CASPubMed Google Scholar
Pearce, E. J., Casper, P., Grzych, J.-M., Lewis, F. A. & Sher, A. Downregulation of TH1 cytokine production accompanies induction of TH2 responses by a parasitic helminth, Schistosoma mansoni. J. Exp. Med.173, 159–166 (1991). CASPubMed Google Scholar
Grzych, J. M. et al. Egg deposition is the major stimulus for the production of TH2 cytokines in murine schistosomiasis mansoni. J. Immunol.146, 1322–1327 (1991).References87and88were the first to show that schistosomiasis leads to the development of a strong TH2 response. CASPubMed Google Scholar
Holland, M. J., Harcus, Y. M., Riches, P. L. & Maizels, R. M. Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for TH2 responses. Eur. J. Immunol.30, 1977–1987 (2000). CASPubMed Google Scholar
Vella, A. T. & Pearce, E. J. CD4+ TH2 response induced by Schistosoma mansoni eggs develops rapidly, through an early, transient, TH0-like stage. J. Immunol.148, 2283–2290 (1992). CASPubMed Google Scholar
Okano, M., Satoskar, A. R., Nishizaki, K., Abe, M. & Harn, D. A. Jr. Induction of TH2 responses and IgE is largely due to carbohydrates functioning as adjuvants on Schistosoma mansoni egg antigens. J. Immunol.163, 6712–6717 (1999).The first report that carbohydrates on egg antigens are important for the induction of TH2 responses. See also reference93. CASPubMed Google Scholar
Williams, D. L., Asahi, H., Botkin, D. J. & Stadecker, M. J. Schistosome infection stimulates host CD4+ T helper cell and B-cell responses against a novel egg antigen, thioredoxin peroxidase. Infect. Immun.69, 1134–1141 (2001). CASPubMedPubMed Central Google Scholar
Okano, M., Satoskar, A. R., Nishizaki, K. & Harn, D. A. Jr. Lacto-N-fucopentaose III found on Schistosoma mansoni egg antigens functions as adjuvant for proteins by inducing TH2-type response. J. Immunol.167, 442–450 (2001). CASPubMed Google Scholar
Figdor, C. G., van Kooyk, Y. & Adema, G. J. C-type lectin receptors on dendritic cells and langerhans cells. Nature Rev. Immunol.2, 77–84 (2002). CAS Google Scholar
Akira, S., Takeda, K. & Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nature Immunol.2, 675–680 (2001). CAS Google Scholar
Schnare, M. et al. Toll-like receptors control activation of adaptive immune responses. Nature Immunol.2, 947–950 (2001). CAS Google Scholar
Whelan, M. et al. A filarial nematode-secreted product signals dendritic cells to acquire a phenotype that drives development of TH2 cells. J. Immunol.164, 6453–6460 (2000). CASPubMed Google Scholar
MacDonald, A. S., Straw, A. D., Bauman, B. & Pearce, E. J. CD8− dendritic-cell activation status plays an integral role in influencing TH2 response development. J. Immunol.167, 1982–1988 (2001). CASPubMed Google Scholar
de Jong, E. C. et al. Microbial compounds selectively induce TH1-cell-promoting or TH2-cell-promoting dendritic cells_in vitro_ with diverse TH-cell-polarizing signals. J. Immunol.168, 1704–1709 (2002). CASPubMed Google Scholar
Kalinski, P., Hilkens, C. M., Wierenga, E. A. & Kapsenberg, M. L. T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol. Today20, 561–567 (1999). CASPubMed Google Scholar
d'Ostiani, C. F. et al. Dendritic cells discriminate between yeasts and hyphae of the fungus Candida albicans. Implications for initiation of T helper cell immunity in vitro and in vivo. J. Exp. Med.191, 1661–1674 (2000). CASPubMedPubMed Central Google Scholar
MacDonald, A. S. & Pearce, E. J. Cutting edge: polarized TH-cell response induction by transferred antigen-pulsed dendritic cells is dependent on IL-4 or IL-12 production by recipient cells. J. Immunol.168, 3127–3130 (2002).A clear demonstration that dendritic cells can interpret pathogen-inherent signals and drive egg-antigen-specific TH2 responses independent of any requirement to make IL-4. See also references97and98. CASPubMed Google Scholar
Jankovic, D. et al. Single-cell analysis reveals that IL-4 receptor/Stat6 signaling is not required for the in vivo or in vitro development of CD4+ lymphocytes with a TH2 cytokine profile. J. Immunol.164, 3047–3055 (2000). CASPubMed Google Scholar
Rincon, M., Anguita, J., Nakamura, T., Fikrig, E. & Flavell, R. A. Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4+ T cells. J. Exp. Med.185, 461–469 (1997). CASPubMedPubMed Central Google Scholar
La Flamme, A. C. & Pearce, E. J. The absence of IL-6 does not affect TH2-cell development in vivo, but does lead to impaired proliferation, IL-2 receptor expression and B-cell responses. J. Immunol.162, 5829–5837 (1999). CASPubMed Google Scholar
La Flamme, A. C., MacDonald, A. S. & Pearce, E. J. Role of IL-6 in directing the initial immune response to schistosome eggs. J. Immunol.164, 2419–2426 (2000). CASPubMed Google Scholar
Harris, D. P. et al. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nature Immunol.1, 475–482 (2000). CAS Google Scholar
Martin, D. L., King, C. L., Pearlman, E., Strine, E. & Heinzel, F. P. IFN-γ is necessary, but not sufficient, for anti-CD40 antibody-mediated inhibition of the TH2 response to Schistosoma mansoni eggs. J. Immunol.164, 779–785 (2000). CASPubMed Google Scholar
van Kooten, C. & Banchereau, J. Functions of CD40 on B cells, dendritic cells and other cells. Curr. Opin. Immunol.9, 330–337 (1997). CASPubMed Google Scholar
MacDonald, A. S., Straw, A. D., Dalton, N. M. & Pearce, E. J. Cutting edge: TH2 response induction by dendritic cells: a role for CD40. J. Immunol.168, 537–540 (2002). CASPubMed Google Scholar
Coyle, A. J. & Gutierrez-Ramos, J. C. The expanding B7 superfamily: increasing complexity in costimulatory signals regulating T-cell function. Nature Immunol.2, 203–209 (2001). CAS Google Scholar
Subramanian, G. et al. B7-2 requirement for helminth-induced granuloma formation and CD4 type-2 T helper cell cytokine expression. J. Immunol.158, 5914–5920 (1997). CASPubMed Google Scholar
Kopf, M. et al. Inducible costimulator protein (ICOS) controls T-helper cell subset polarization after virus and parasite infection. J. Exp. Med.192, 53–61 (2000). CASPubMedPubMed Central Google Scholar
Xu, D. et al. Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. J. Exp. Med.187, 787–794 (1998). CASPubMedPubMed Central Google Scholar
Tesciuba, A. G. et al. Inducible costimulator regulates TH2-mediated inflammation, but not TH2 differentiation, in a model of allergic airway disease. J. Immunol.167, 1996–2003 (2001). CASPubMed Google Scholar
Lohning, M. et al. T1/ST2 expression is enhanced on CD4+ T cells from schistosome egg-induced granulomas: analysis of TH-cell cytokine coexpression ex vivo. J. Immunol.162, 3882–3889 (1999). CASPubMed Google Scholar
Townsend, M. J., Fallon, P. G., Matthews, D. J., Jolin, H. E. & McKenzie, A. N. T1/ST2-deficient mice demonstrate the importance of T1/ST2 in developing primary T helper cell type-2 responses. J. Exp. Med.191, 1069–1076 (2000). CASPubMedPubMed Central Google Scholar
Capron, A., Capron, M., Dombrowicz, D. & Riveau, G. Vaccine strategies against schistosomiasis: from concepts to clinical trials. Int. Arch. Allergy Immunol.124, 9–15 (2001). CASPubMed Google Scholar
Bergquist, N. & Colley, D. Schistosomiasis vaccines: research to development. Parasitol. Today14, 99–104 (1998). CASPubMed Google Scholar
Pearce, E. Progress towards a vaccine for schistosomiasis. Acta Tropica (in the press).
Wilson, R. A., Coulson, P. S. & Mountford, A. P. Immune responses to the radiation-attenuated schistosome vaccine: what can we learn from knock-out mice? Immunol. Lett.65, 117–123 (1999). CASPubMed Google Scholar
Wynn, T. A. & Hoffmann, K. F. Defining a schistosomiasis vaccination strategy — is it really TH1 versus TH2? Parasitol. Today16, 497–501 (2000). CASPubMed Google Scholar
Caulada-Benedetti, Z., al-Zamel, F., Sher, A. & James, S. Comparison of TH1- and TH2-associated immune reactivities stimulated by single versus multiple vaccination of mice with irradiated Schistosoma mansoni cercariae. J. Immunol.146, 1655–1660 (1991). CASPubMed Google Scholar
Oswald, I. P., Wynn, T. A., Sher, A. & James, S. L. NO as an effector molecule of parasite killing: modulation of its synthesis by cytokines. Comp. Biochem. Physiol. Pharmacol. Toxicol. Endocrinol.108, 11–18 (1994). CASPubMed Google Scholar
Street, M. et al. TNF is essential for the cell-mediated protective immunity induced by the radiation-attenuated schistosome vaccine. J. Immunol.163, 4489–4494 (1999). CASPubMed Google Scholar
Wilson, R. A., Coulson, P. S., Betts, C., Dowling, M. A. & Smythies, L. E. Impaired immunity and altered pulmonary responses in mice with a disrupted interferon-γ receptor gene exposed to the irradiated Schistosoma mansoni vaccine. Immunology87, 275–282 (1996). CASPubMedPubMed Central Google Scholar
Jankovic, D. et al. Optimal vaccination against Schistosoma mansoni requires the induction of both B-cell- and IFN-γ-dependent effector mechanisms. J. Immunol.162, 345–351 (1999). CASPubMed Google Scholar
Wynn, T. A. et al. IL-12 enhances vaccine-induced immunity to schistosomes by augmenting both humoral and cell-mediated immune responses against the parasite. J. Immunol.157, 4068–4078 (1996). CASPubMed Google Scholar
Chiaramonte, M. G., Hesse, M., Cheever, A. W. & Wynn, T. A. CpG oligonucleotides can prophylactically immunize against TH2-mediated schistosome egg-induced pathology by an IL-12-independent mechanism. J. Immunol.164, 973–985 (2000). CASPubMed Google Scholar
Anderson, S., Shires, V. L., Wilson, R. A. & Mountford, A. P. In the absence of IL-12, the induction of TH1-mediated protective immunity by the attenuated schistosome vaccine is impaired, revealing an alternative pathway with TH2-type characteristics. Eur. J. Immunol.28, 2827–2838 (1998). CASPubMed Google Scholar
Mangold, B. L. & Dean, D. A. The role of IgG antibodies from irradiated cercaria-immunized rabbits in the passive transfer of immunity to _Schistosoma mansoni_-infected mice. Am. J. Trop. Med. Hyg.47, 821–829 (1992). CASPubMed Google Scholar
Hoffmann, K. F., James, S. L., Cheever, A. W. & Wynn, T. A. Studies with double cytokine-deficient mice reveal that highly polarized TH1- and TH2-type cytokine and antibody responses contribute equally to vaccine-induced immunity to Schistosoma mansoni. J. Immunol.163, 927–938 (1999). CASPubMed Google Scholar
Doenhoff, M., Kimani, G. & Cioli, D. Praziquantel and the control of schistosomiasis. Parasitol. Today16, 364–366 (2000). CASPubMed Google Scholar
Wynn, T. A. Development of an antipathology vaccine for schistosomiasis. Ann. NY Acad. Sci.797, 191–195 (1996). CASPubMed Google Scholar
Stadecker, M. J. The regulatory role of the antigen-presenting cell in the development of hepatic immunopathology during infection with Schistosoma mansoni. Pathobiology67, 269–272 (1999). CASPubMed Google Scholar
Pearce, E. J. & Sher, A. Mechanisms of immune evasion in schistosomiasis. Contrib. Microbiol. Immunol.8, 219–232 (1987). CASPubMed Google Scholar
Colley, D. G., LoVerde, P. T. & Savioli, L. Infectious disease. Medical helminthology in the 21st century. Science293, 1437–1438 (2001). CASPubMed Google Scholar
Cribb, T. A., Bray, R. A., Littlewood, T., Pichelin, S. P. & Herniou, E. A. In Interrelationships of the Platyhelminthes (eds Littlewood, D. T. J. & Bray, R. A.) 168–185 (Taylor & Francis, London, 2001). Google Scholar
Agnew, A. M., Murare, H. M. & Doenhoff, M. J. Immune attrition of adult schistosomes. Parasite Immunol.15, 261–271 (1993). CASPubMed Google Scholar
Doenhoff, M. J. A role for granulomatous inflammation in the transmission of infectious disease: schistosomiasis and tuberculosis. Parasitology115, S113–S125 (1997). PubMed Google Scholar
Karanja, D. M., Colley, D. G., Nahlen, B. L., Ouma, J. H. & Secor, W. E. Studies on schistosomiasis in western Kenya. I. Evidence for immune-facilitated excretion of schistosome eggs from patients with Schistosoma mansoni and human immunodeficiency virus coinfections. Am. J. Trop. Med. Hyg.56, 515–521 (1997). CASPubMed Google Scholar
Ngaiza, J. R. & Doenhoff, M. J. Blood platelets and schistosome egg excretion. Proc. Soc. Exp. Biol. Med.193, 73–79 (1990). CASPubMed Google Scholar
Ishii, A. et al. Parasite infection and cancer: with special emphasis on Schistosoma japonicum infections (Trematoda). A review. Mutat. Res.305, 273–281 (1994). CASPubMed Google Scholar
Feldmeier, H., Leutscher, P., Poggensee, G. & Harms, G. Male genital schistosomiasis and haemospermia. Trop. Med. Int. Health4, 791–793 (1999). CASPubMed Google Scholar
Poggensee, G., Krantz, I., Kiwelu, I., Diedrich, T. & Feldmeier, H. Presence of Schistosoma mansoni eggs in the cervix uteri of women in Mwanga District, Tanzania. Trans. R. Soc. Trop. Med. Hyg.95, 299–300 (2001). CASPubMed Google Scholar
Fallon, P. G. & Dunne, D. W. Tolerization of mice to Schistosoma mansoni egg antigens causes elevated type 1 and diminished type 2 cytokine responses and increased mortality in acute infection. J. Immunol.162, 4122–4132 (1999). CASPubMed Google Scholar
Dunne, D. W. & Doenhoff, M. J. Schistosoma mansoni egg antigens and hepatocyte damage in infected T-cell-deprived mice. Contrib. Microbiol. Immunol.7, 22–29 (1983). CASPubMed Google Scholar
Read, S. & Powrie, F. CD4+ regulatory T cells. Curr. Opin. Immunol.13, 644–649 (2001). CASPubMed Google Scholar
Angeli, V. et al. Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection. J. Exp. Med.193, 1135–1147 (2001). CASPubMedPubMed Central Google Scholar
Fallon, P. G. Immunopathology of schistosomiasis: a cautionary tale of mice and men. Immunol. Today21, 29–35 (2000). CASPubMed Google Scholar