Source: http://www.asmscience.org/content/book/10.1128/9781555816872.ch25
Timestamp: 2019-04-21 02:26:35+00:00

Document:
The strongest indication that acquired immunity to helminth infections may develop in humans comes from the changing patterns of infection with age. Eosinophils, a characteristic feature of the Th2 response to helminths, have long been associated with enhanced killing of larval schistosomes, with recent studies demonstrating greater immunity in eosinophilic humans. Our understanding of acquired immunity to helminths is based on a rich substrate of animal models, most importantly, the mouse. It is entirely plausible that the halting nature of human immunity to helminths can be ascribed to the strength of regulatory restraints that have evolved to minimize pathological outcomes. The influence of mast cells on immunity to intestinal nematode infection is species specific. In addition to recruitment of inflammatory cells, expulsion of most intestinal nematodes is commonly associated with dramatic alterations in IEC proliferation, turnover, and/or differentiation. Changes in glycosylation status of mucins also occur following intestinal nematode infection, although at present, there is limited evidence to support a direct role for mucins in expulsion of intestinal nematode parasites. Successful resolution of helminth infections requires the appropriate mode and degree of immune responsiveness if full immunity is to be achieved without severe pathological consequences.
Initiation and regulation of parasite-specific Th2 cell responses following exposure to intestinal nematode infection. Following infection with intestinal nematode parasites, intestinal epithelial cells express a wide range of chemokines and immunoregulatory cytokines, including IL-17E, thymic stromal lymphopoietin (TSLP), and IL-33. These cytokines can promote expression of IL-4 and/or IL-13 in granulocyte populations including mast cells (MC), eosinophils (EOS), and basophils (BASO). IL-17E and TSLP can also create a permissive environment for Th2 cell differentiation by limiting expression of proinflammatory cytokines in dendritic cells (DCs). Naïve CD4+T cells are activated in the draining mesenteric lymph nodes and, in the presence of the appropriate signals, differentiate into host protective Th2 cells that express IL-4, IL-5, IL-9, IL-13, and IL-17E.
Th2 cell-mediated immune effector mechanisms in expulsion of intestinal nematode infection. Th2 cell-derived cytokines can promote granulocyte activation including expression of IL-4, MHC class II, costimulatory molecules, and mouse mast cell protease (MMCP). In addition, Th2 cytokines can promote alternative activation of macrophages (AAMac) that express chitinases, chitinase-like molecules (YM-1), arginase-1, and RELMα that can promote parasite expulsion, wound healing, and can limit the magnitude of Th2 cytokine responses. Th2 cells can also influence nonhematopoietic cell lineages, including promoting smooth muscle contractility and alterations in intestinal epithelial cell (IEC) proliferation, differentiation, and migration. Therefore, parasite-specific CD4+ T cells elicit nonparasite-specific inflammation and changes in intestinal physiology that create an environment that is unfavorable for parasite persistence. The relative importance of each pathway depends on the particular species of nematode parasite that infects the host.
1. Anthony, R. M.,, J. F. Urban, Jr.,, F. Alem,, H. A. Hamed,, C. T. Rozo,, J. L. Boucher,, N. Van Rooijen, and, W. C. Gause. 2006. Memory Th2 cells induce alternatively activated macrophages to mediate protection against nematode parasites. Nat. Med. 12: 955– 960.
2. Anthony, R. M.,, L. I. Rutitzky,, J. F. Urban, Jr.,, M. J. Stadecker, and, W. C. Gause. 2007. Protective immune mechanisms in helminth infection. Nat. Rev. Immunol. 7: 975– 987.
3. Artis, D. 2006. New weapons in the war on worms: identification of putative mechanisms of immune-mediated expulsion of gastrointestinal nematodes. Int. J. Parasitol. 36: 723– 733.
4. Artis, D. 2008. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat. Rev. Immunol. 8: 411– 420.
5. Artis, D., and, R. K. Grencis. 2008. The intestinal epithelium: sensors to effectors in nematode infection. Mucosal Immunol. 1: 252– 264.
6. Babu, S.,, C. P. Blauvelt,, V. Kumaraswami, and, T. B. Nutman. 2006. Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. J. Immunol. 176: 3248– 3256.
7. Babu, S.,, S. Q. Bhat,, N. Pavan Kumar,, A. B. Lipira,, S. Kumar,, C. Karthik,, V. Kumaraswami, and, T. B. Nutman. 2009. Filarial lymphedema is characterized by antigen-specific Th1 and th17 proinflammatory responses and a lack of regulatory T cells. PLoS Negl. Trop. Dis. 3: e420.
8. Bradley, J. E., and, J. A. Jackson. 2004. Immunity, immunoregulation and the ecology of trichuriasis and ascariasis. Parasite Immunol. 26: 429– 441.
9. Bundy, D. A. P., and, G. F. Medley. 1992. Immuno-epidemiology of human geohelminthiasis: ecological and immunological determinants of worm burden. Parasitology 104: 105– 119.
10. Cadman, E. T., and, R. A. Lawrence. 2010. Granulocytes: effector cells or immunomodulators in the immune response to helminth infection? Parasite Immunol. 32: 1– 19.
11. Capron, A.,, J.-P. Dessaint,, M. Capron,, M. Joseph, and, G. Torpier. 1982. Effector mechanisms of immunity to schistosomes and their regulation. Immunol. Rev. 61: 41– 66.
12. Cliffe, L. J., and, R. K. Grencis. 2004. The Trichuris muris system: a paradigm of resistance and susceptibility to intestinal nematode infection. Adv. Parasitol. 57: 255– 307.
13. Cliffe, L. J.,, N. E. Humphreys,, T. E. Lane,, C. S. Potten,, C. Booth, and, R. K. Grencis. 2005. Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion. Science 308: 1463– 1465.
14. Daly, C. M.,, G. Mayrhofer, and, L. A. Dent. 1999. Trapping and immobilization of Nippostrongylus brasiliensis larvae at the site of inoculation in primary infections of interleukin-5 transgenic mice. Infect. Immun. 67: 5315– 5323.
15. Day, K. P.,, B. Grenfell,, R. Spark,, J. W. Kazura, and, M. P. Alpers. 1991. Age specific patterns of change in the dynamics of Wuchereria bancrofti infection in Papua New Guinea. Am. J. Trop. Med. Hyg. 44: 518– 527.
16. Dessein, A.,, B. Kouriba,, C. Eboumbou,, H. Dessein,, L. Argiro,, S. Marquet,, N. E. Elwali,, V. Rodrigues,, Y. Li,, O. Doumbo, and, C. Chevillard. 2004. Interleukin-13 in the skin and interferon-gamma in the liver are key players in immune protection in human schistosomiasis. Immunol. Rev. 201: 180– 190.
17. Else, K. J., and, F. D. Finkelman. 1998. Intestinal nematode parasites, cytokines and effector mechanisms. Int. J. Parasitol. 28: 1145– 1158.
18. Else, K. J. 2002. Chemokines and leucocyte migration in parasitic disease. Parasite Immunol. 24: 281– 283.
19. Fabre, V.,, D. P. Beiting,, S. K. Bliss,, N. G. Gebreselassie,, L. F. Gagliardo,, N. A. Lee,, J. J. Lee, and, J. A. Appleton. 2009. Eosinophil deficiency compromises parasite survival in chronic nematode infection. J. Immunol. 182: 1577– 1583.
20. Finkelman, F. D.,, T. Shea-Donohue,, J. Goldhill,, C. A. Sullivan,, S. C. Morris,, K. B. Madden,, W. C. Gause, and, J. F. Urban, Jr. 1997. Cytokine regulation of host defense against parasitic gastrointestinal nematodes: lessons from studies with rodent models. Annu. Rev. Immunol 15: 505– 533.
21. Finkelman, F. D.,, T. Shea-Donohue,, S. C. Morris,, L. Gildea,, R. Strait,, K. B. Madden,, L. Schopf, and, J. F. Urban, Jr. 2004. Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites. Immunol. Rev. 201: 139– 155.
22. Fujiwara, R. T.,, A. Loukas,, S. Mendez,, A. L. Williamson,, L. L. Bueno,, Y. Wang,, A. Samuel,, B. Zhan,, M. E. Bottazzi,, P. J. Hotez, and, J. M. Bethony. 2006. Vaccination with irradiated Ancylostoma caninum third stage larvae induces a Th2 protective response in dogs. Vaccine 24: 501– 509.
23. Ganley-Leal, L. M.,, P. N. Mwinzi,, C. B. Cetre-Sossah,, J. Andove,, A. W. Hightower,, D. M. Karanja,, D. G. Colley, and, W. E. Secor. 2006. Correlation between eosinophils and protection against reinfection with Schistosoma mansoni and the effect of human immunodeficiency virus type 1 coinfection in humans. Infect. Immun. 74: 2169– 2176.
24. Gray, C. A., and, R. A. Lawrence. 2002. A role for antibody and Fc receptor in the clearance of Brugia malayi microfilariae. Eur. J. Immunol. 32: 1114– 1120.
25. Grencis, R. K. 1997a. Enteric helminth infection: immunopathology and resistance during intestinal nematode infection. Chem. Immunol. 66: 41– 61.
26. Grencis, R. K. 1997b. Th2-mediated host protective immunity to intestinal nematode infections. Philosophical Transactions of the Royal Society, Series B 352: 1377– 1384.
27. Grencis, R. K., and, A. J. Bancroft. 2004. Interleukin-13: a key mediator in resistance to gastrointestinal-dwelling nematode parasites. Clin. Rev. Allergy Immunol. 26: 51– 60.
28. Grencis, R. K.,, K. J. Else,, J. F. Huntley, and, S. I. Nishikawa. 1993. The in viro role of stem cell factor (c-kit ligand) on mastocytosis and host protective immunity to the intestinal nematode Trichinella spiralis in mice. Parasite Immunol. 15: 55– 59.
29. Hagan, P.,, U. J. Blumenthal,, D. Dunn,, A. J. G. Simpson, and, H. A. Wilkins. 1991. Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature 349: 243– 245.
30. Herbert, D. R.,, J.-Q. Yang,, S. P. Hogan,, K. Groschwitz,, M. V. Khodoun,, A. Munitz,, T. Orekov,, C. Perkins,, Q. Wang,, F. Brombacher,, J. F. Urban,, M. E. Rothenberg, and, F. D. Finkelman. 2009. Intestinal epithelial cell secretion of RELM- β protects against gastrointestinal worm infection. J. Exp. Med. 206: 2947– 2957.
31. Hotez, P. J.,, P. J. Brindley,, J. M. Bethony,, C. H. King,, E. J. Pearce, and, J. Jacobson. 2008. Helminth infections: the great neglected tropical diseases. J. Clin. Invest. 118: 1311– 1321.
32. Jackson, J. A.,, J. D. Turner,, L. Rentoul,, H. Faulkner,, J. M. Behnke,, M. Hoyle,, R. K. Grencis,, K. J. Else,, J. Kamgno,, M. Boussinesq, and, J. E. Bradley. 2004. T helper cell type 2 responsiveness predicts future susceptibility to gastrointestinal nematodes in humans. J. Infect. Dis. 190: 1804– 1811.
33. James, S. L., and, J. Glaven. 1989. Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates. J. Immunol. 143: 4208– 4212.
34. King, C. L.,, S. Mahanty,, V. Kumaraswami,, J. S. Abrams,, J. Regunathan,, K. Jayaraman,, E. A. Ottesen, and, T. B. Nutman. 1993. Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J. Clin. Invest. 92: 1667– 1673.
35. Knott, M. L.,, K. I. Matthaei,, P. R. Giacomin,, H. Wang,, P. S. Foster, and, L. A. Dent. 2007. Impaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis. Int. J. Parasitol. 37: 1367– 1378.
36. MacDonald, A. S.,, R. M. Maizels,, R. A. Lawrence,, I. Dransfield, and, J. E. Allen. 1998. Requirement for in vivo production of IL-4, but not IL-10, in the induction of proliferative suppression by filarial parasites. J. Immunol. 160: 4124– 4132.
37. Maizels, R. M., and, M. Yazdanbakhsh. 2003. Regulation of the immune response by helminth parasites: cellular and molecular mechanisms. Nat. Rev. Immunol. 3: 733– 743.
38. Maizels, R. M.,, A. Balic,, N. Gomez-Escobar,, M. Nair,, M. Taylor, and, J. E. Allen. 2004. Helminth parasites: masters of regulation. Immunol. Rev. 201: 89– 116.
39. McDermott, J. R.,, R. E. Bartram,, P. A. Knight,, H. R. Miller,, D. R. Garrod, and, R. K. Grencis. 2003. Mast cells disrupt epithelial barrier function during enteric nematode infection. Proc. Natl. Acad. Sci. USA 100: 7761– 7766.
40. Miller, H. R. 1996. Mucosal mast cells and the allergic response against nematode parasites. Vet. Immunol. Immunopathol. 54: 331– 336.
41. Mountford, A. P., and, F. Trottein. 2004. Schistosomes in the skin: a balance between immune priming and regulation. Trends Parasitol. 20: 221– 226.
42. Nair, M. G.,, K. J. Guild, and, D. Artis. 2006. Novel effector molecules in type 2 inflammation: lessons drawn from helminth infection and allergy. J. Immunol. 177: 1393– 1399.
43. Ohnmacht, C., and, D. Voehringer. 2010. Basophils protect against reinfection with hookworms independently of mast cells and memory Th2 cells. J. Immunol. 184: 344– 350.
44. Patel, N.,, T. Kreider,, J. F. Urban, Jr., and, W. C. Gause. 2009. Characterisation of effector mechanisms at the host:parasite interface during the immune response to tissue-dwelling intestinal nematode parasites. Int. J. Parasitol. 39: 13– 21.
45. Pearce, E. J., and, A. S. MacDonald. 2002. The immunobiology of schistosomiasis. Nat. Rev. Immunol. 2: 499– 511.
46. Pennock, J. L., and, R. K. Grencis. 2006. The mast cell and gut nematodes: damage and defence. Chem. Immunol. Allergy 90: 128– 140.
47. Perrigoue, J. G.,, F. A. Marshall, and, D. Artis. 2008. On the hunt for helminths: innate immune cells in the recognition and response to helminth parasites. Cell Microbiol. 10: 1757– 1764.
48. Pesce, J. T.,, T. R. Ramalingam,, M. M. Mentink-Kane,, M. S. Wilson,, K. C. El Kasmi,, A. M. Smith,, R. W. Thompson,, A. W. Cheever,, P. J. Murray, and, T. A. Wynn. 2009a. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog. 5: e1000371.
49. Pesce, J. T.,, T. R. Ramalingam,, M. S. Wilson,, M. M. Mentink-Kane,, R. W. Thompson,, A. W. Cheever,, J. F. Urban, Jr., and, T. A. Wynn. 2009b. Retnla (relma/fizz1) suppresses helminth-induced Th2-type immunity. PLoS Pathog. 5: e1000393.
50. Quinnell, R. J. 2003. Genetics of susceptibility to human helminth infection. Int. J. Parasitol. 33: 1219– 1231.
51. Rajan, B.,, T. Ramalingam, and, T. V. Rajan. 2005. Critical role for IgM in host protection in experimental filarial infection. J. Immunol. 175: 1827– 1833.
52. Rodriguez-Sosa, M.,, A. R. Satoskar,, J. R. David, and, L. I. Terrazas. 2003. Altered T helper responses in CD40 and interleukin-12 deficient mice reveal a critical role for Th1 responses in eliminating the helminth parasite Taenia crassiceps. Int. J. Parasitol. 33: 703– 711.
53. Rotman, H. L.,, W. Yutanawiboonchai,, R. A. Brigandi,, O. Leon,, G. J. Gleich,, T. J. Nolan,, G. A. Schad, and, D. Abraham. 1996. Strongyloides stercoralis: eosinophil-dependent immune-mediated killing of third stage larvae in BALB/cByJ mice. Exp. Parasitol. 82: 267– 278.
54. Saeftel, M.,, M. Arndt,, S. Specht,, L. Volkmann, and, A. Hoerauf. 2003. Synergism of gamma interferon and interleukin-5 in the control of murine filariasis. Infect. Immun. 71: 6978– 6985.
55. Saenz, S. A.,, B. C. Taylor, and, D. Artis. 2008. Welcome to the neighborhood: epithelial cell-derived cytokines license innate and adaptive immune responses at mucosal sites. Immunol. Rev. 226: 172– 190.
56. Sartono, E.,, Y. C. M. Kruize,, A. Kurniawan-Atmadja,, R. M. Maizels, and, M. Yazdanbakhsh. 1997. Depression of antigen-specific interleukin-5 and interferon-γ responses in human lymphatic filariasis as a function of clinical status and age. J. Infect. Dis. 175: 1276– 1280.
57. Satoguina, J. S.,, E. Weyand,, J. Larbi, and, A. Hoerauf. 2005. T regulatory-1 cells induce IgG4 production by B cells: role of IL-10. J. Immunol. 174: 4718– 4726.
58. Schramm, G.,, K. Mohrs,, M. Wodrich,, M. J. Doenhoff,, E. J. Pearce,, H. Haas, and, M. Mohrs. 2007. 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– 6027.
59. Sher, A.,, R. L. Coffman,, S. Hieny, and, A. W. Cheever. 1990. Ablation of eosinophil and IgE responses with anti-IL-5 or anti-IL-4 antibodies fails to affect immunity against Schistosoma mansoni in the mouse. J. Immunol. 145: 3911– 3916.
60. Simons, J. E.,, M. E. Rothenberg, and, R. A. Lawrence. 2005. Eotaxin-1-regulated eosinophils have a critical role in innate immunity against experimental Brugia malayi infection. Eur. J. Immunol. 35: 189– 197.
61. Stetson, D. B.,, D. Voehringer,, J. L. Grogan,, M. Xu,, R. L. Reinhardt,, S. Scheu,, B. L. Kelly, and, R. M. Locksley. 2004. Th2 cells: orchestrating barrier immunity. Adv. Immunol. 83: 163– 189.
62. Sullivan, B. M., and, R. M. Locksley. 2009. Basophils: a nonredundant contributor to host immunity. Immunity 30: 12– 20.
63. Taylor, M. D.,, A. Harris,, M. G. Nair,, R. M. Maizels, and, J. E. Allen. 2006. F4/80 + alternatively activated macrophages control CD4 + T cell hyporesponsiveness at sites peripheral to filarial infection. J. Immunol. 176: 6918– 6927.
64. Turner, J.,, H. Faulkner,, J. Kamgno,, F. Cormont,, J. Van Snick,, K. Else,, R. Grencis,, J. Behnke,, M. Boussinesq, and, J. E. Bradley. 2003. Th2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection. J. Infect. Dis. 188: 1768– 1775.
65. Urban, J. F.,, K. B. Madden,, A. Svetica,, A. Cheever,, P. P. Trotta,, W. C. Gause,, I. M. Katona, and, F. D. Finkelman. 1992. The importance of Th2 cytokines in protective immunity to nematodes. Immunol. Rev. 127: 205– 220.
66. Walter, K.,, A. J. Fulford,, R. McBeath,, S. Joseph,, F. M. Jones,, H. C. Kariuki,, J. K. Mwatha,, G. Kimani,, N. B. Kabatereine,, B. J. Vennervald,, J. H. Ouma, and, D. W. Dunne. 2006. Increased human IgE induced by killing Schistosoma mansoni in vivo is associated with pretreatment Th2 cytokine responsiveness to worm antigens. J. Immunol. 177: 5490– 5498.
67. Wojciechowski, W.,, D. P. Harris,, F. Sprague,, B. Mousseau,, M. Makris,, K. Kusser,, T. Honjo,, K. Mohrs,, M. Mohrs,, T. Randall, and, F. E. Lund. 2009. Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus. Immunity 30: 1– 13.
68. Woolhouse, M. E. 1992. A theoretical framework for the immunoepidemiology of helminth infection. Parasite Immunol. 14: 563– 578.
69. Zhang, W.,, A. G. Ross, and, D. P. McManus. 2008. Mechanisms of immunity in hydatid disease: implications for vaccine development. J. Immunol. 181: 6679– 6685.

References: V. 
 V. 
 V. 
 V. 
 V. 
 V.