Chapter 17 : Adaptive Immune Effector Mechanisms against Intracellular Protozoa and Gut-Dwelling Nematodes

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This chapter covers the acquired immune responses to two types of parasites. The first is the immune response associated with intracellular protozoa, and the principal examples will be , , and . The chapter then discusses the immune responses associated with control of helminth infections, particularly focusing on gut-dwelling nematodes. The current model for macrophage activation is that IFN-γ primes cells, and additional signals, such as tumor necrosis factor (TNF), trigger activation of the cell. The relative importance of IL-4 and IL-13 in resistance is also influenced by host genetic background and highlighted by studies in the system. Here, IL-4KO mice on a C57BL/6 background are uniformly susceptible and develop chronic infections whereas WT mice expel their worm burden. This chapter reviews the effector mechanisms associated with resistance to a select group of parasites, particularly focusing on parasites that illustrate the diversity of effector mechanisms contributing to protective immunity. The immune responses required for eliminating intracellular protozoa are quite different from those required to control gut-dwelling nematodes and can be divided into type 1 and type 2 responses. However, while type 1 or type 2 responses may dominate following infection with intracellular protozoa or gut-dwelling nematodes, respectively, the effector mechanisms required for resistance to any one particular parasite are often tailored to the biological characteristics of that parasite, which in some cases remain to be defined.

Citation: Scott P, Grencis R. 2002. Adaptive Immune Effector Mechanisms against Intracellular Protozoa and Gut-Dwelling Nematodes, p 235-246. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch17
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1. Abe, T.,, H. Sugaya,, K. Yoshimura,, and Y. Nawa. 1992. Induction of the expulsion of Strongyloides ratti and retention of Nippostrongylus brasiliensis in athymic nude mice by repetitive administration of recombinant interleukin-3. Immunology 76: 10 14.
2. Ahmad, A.,, C. H. Wang,, and R. G. Bell. 1991. A role for IgE in intestinal immunity. Expression of rapid expulsion of Trichinella spiralis in rats transfused with IgE and thoracic duct lymphocytes. J. Immunol. 146: 3563 3570.
3. Aliberti, J.,, C. Reis e Sousa,, M. Schito,, S. Hieny,, T. Wells,, G. B. Huffnagel,, and A. Sher. 2000. CCR5 provides a signal for microbial induced production of IL-12 by CD8a+ dendritic cells. Nat. Immunol. 1: 83 87.
4. Alizadeh, H.,, and K. D. Murrell. 1984. The intestinal mast cell response to Trichinella spiralis infection in mast cell-deficient w/wv mice. J. Parasitol. 70: 767 773.
5. Appleton, J. A.,, and D. D. McGregor. 1987. Characterization of the immune mediator of rapid expulsion of Trichinella spiralis in suckling rats. Immunology 62: 477 484.
6. Artis, D.,, N. E. Humphreys,, A. J. Bancroft,, N. J. Rothwell,, C. S. Potten,, and R. K. Grencis. 1999. Tumor necrosis factor alpha is a critical component of interleukin 13-mediated protective T helper cell type 2 responses during helminth infection. J. Exp. Med. 190: 953 962.
7. Bancroft, A. J.,, D. Artis,, D. D. Donaldson,, J. P. Sypek,, and R. K. Grencis. 2000. Gastrointestinal nematode expulsion in IL-4 knockout mice is IL-13 dependent. Eur. J. Immunol. 30: 2083 2091.
8. Bancroft, A. J.,, K. J. Else,, J. P. Sypek,, and R. K. Grencis. 1997. Interleukin-12 promotes a chronic intestinal nematode infection. Eur. J. Immunol. 27: 866 870.
9. Barner, M.,, M. Mohrs,, F. Brombacher,, and M. Kopf. 1998. Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses. Curr. Biol. 8: 669 672.
10. Behm, C. A.,, and K. S. Ovington. 2000. The role of eosinophils in parasitic helminth infections: insights from genetically modified mice. Parasitol. Today 16: 202 209.
11. Behnke, J. M.,, C. J. Barnard,, and D. Wakelin. 1992. Understanding chronic nematode infections: evolutionary considerations, current hypotheses and the way forward. Int. J. Parasitol. 22: 861 907.
12. Betts, C. J.,, and K. J. Else. 1999. Mast cells, eosinophils and antibody- mediated cellular cytotoxicity are not critical in resistance to Trichuris muris. Parasite Immunol. 21: 45 52.
13. Bogdan, C.,, and M. Rollinghoff. 1999. How do protozoan parasites survive inside macrophages? Parasitol. Today 15: 22 28.
14. Brown, D. R.,, and S. L. Reiner 1999. Polarized helper-T-cell responses against Leishmania major in the absence of B cells. Infect. Immun. 67: 266 270.
15. Campbell, K. A.,, P. J. Ovendale,, M. K. Kennedy,, W. C. Fanslow,, S. G. Reed,, and C. R. Maliszewski. 1996. CD40 ligand is required for protective cell-mediated immunity to Leishmania major. Immunity 4: 283 290.
16. Carrera, L.,, R. T. Gazzinelli,, R. Badolato,, S. Hieny,, W. Muller,, R. Kuhn,, and D. L. Sacks. 1996. Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice. J. Exp. Med. 183: 515 526.
17. Castro, G. A.,, J. J. Hessel,, and G. Whalen. 1979. Altered intestinal fluid movement in response to Trichinella spiralis in immunized rats. Parasite Immunol. 1: 259 266.
18. Ceravolo, I. P.,, A. C. Chaves,, C. A. Bonjardim,, D. Sibley,, A. J. Romanha,, and R. T. Gazzinelli. 1999. Replication of Toxoplasma gondii, but not Trypanosoma cruzi, is regulated in human fibroblasts activated with gamma interferon: requirement of a functional JAK/STAT pathway. Infect. Immun. 67: 2233 2240.
19. Chan, M. S. 1997. The global burden of intestinal nematode infections— fifty years on. Parasitol. Today 13: 438 443.
20. Coffman, R. L.,, B. W. Seymour,, S. Hudak,, J. Jackson,, and D. Rennick. 1989. Antibody to interleukin-5 inhibits helminthinduced eosinophilia in mice. Science 245: 308 310.
21. Crowle, P. K.,, and N. D. Reed. 1981. Rejection of the intestinal parasite Nippostrongylus brasiliensis by mast cell-deficient W/Wv anemic mice. Infect. Immun. 33: 54 58.
22. Denkers, E. Y.,, and R. T. Gazzinelli. 1998. Regulation and function of T-cell-mediated immunity during Toxoplasma gondii infection. Clin. Microbiol. Rev. 11: 569 588.
23. Denkers, E. Y.,, G. Yap,, T. Scharton-Kersten,, H. Charest,, B. A. Butcher,, P. Caspar,, S. Heiny,, and A. Sher. 1997. Perforinmediated cytolysis plays a limited role in host resistance to Toxoplasma gondii. J Immunol. 159: 1903 1908.
24. Dessein, A. J.,, W. L. Parker,, S. L. James,, and J. R. David. 1981. IgE antibody and resistance to infection. I. Selective suppression of the IgE antibody response in rats diminishes the resistance and the eosinophil response to Trichinella spiralis infection. J. Exp. Med. 153: 423 436.
25. Donaldson, L. E.,, E. Schmitt,, J. F. Huntley,, G. F. Newlands,, and R. K. Grencis. 1996. A critical role for stem cell factor and ckit in host protective immunity to an intestinal helminth. Int. Immunol. 8: 559 567.
26. Ehigiator, H. N.,, A. W. Stadnyk,, and T. D. Lee. 2000. Modulation of B-cell proliferative response by a soluble extract of Nippostrongylus brasiliensis. Infect Immun. 68: 6154 6161.
27. Else, K. J.,, and F. D. Finkelman. 1998. Intestinal nematode parasites, cytokines and effector mechanisms. Int. J. Parasitol. 28: 1145 1158.
28. Else, K. J.,, F. D. Finkelman,, C. R. Maliszewski,, and R. K. Grencis. 1994. Cytokine-mediated regulation of chronic intestinal helminth infection. J. Exp. Med. 179: 347 351.
29. Else, K. J.,, and R. K. Grencis. 1996. Antibody-independent effector mechanisms in resistance to the intestinal nematode parasite Trichuris muris. Infect. Immun. 64: 2950 2954.
30. Else, K. J.,, D. Wakelin,, D. L. Wassom,, and K. M. Hauda. 1990. MHC-restricted antibody responses to Trichuris muris excretory / secretory (E / S) antigen. Parasite Immunol. 12: 509 527.
31. Farrell, J. P.,, I. Muller,, and J. A. Louis. 1989. A role for Lyt2+ T cells in resistance to cutaneous leishmaniasis in immunized mice. J. Immunol. 142: 2052 2056.
32. Faulkner, H.,, N. Humphreys,, J. C. Renauld,, J. Van Snick,, and R. Grencis. 1997. Interleukin-9 is involved in host protective immunity to intestinal nematode infection. Eur. J. Immunol. 27: 2536 2540.
33. Faulkner, H.,, J. C. Renauld,, J. Van Snick,, and R. K. Grencis. 1998. Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris. Infect Immun. 66: 3832 3840.
34. Finkelman, F. D.,, K. B. Madden,, A. W. Cheever,, I. M. Katona,, S. C. Morris,, M. K. Gately,, B. R. Hubbard,, W. C. Gause,, and J. F. Urban, Jr. 1994. Effects of interleukin 12 on immune responses and host protection in mice infected with intestinal nematode parasites. J. Exp. Med. 179: 1563 1572.
35. Finkelman, F. D.,, S. C. Morris,, T. Orekhova,, M. Mori,, D. Donaldson,, S. L. Reiner,, N. L. Reilly,, L. Schopf,, and J. F. Urban, Jr. 2000. Stat6 regulation of in vivo IL-4 responses. J. Immunol. 164: 2303 2310.
36. 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.
37. Grencis, R. K. 1997. Enteric helminth infection: immunopathology and resistance during intestinal nematode infection. Chem. Immunol. 66: 41 61.
38. Grencis, R. K.,, and G. M. Entwistle. 1997. Production of an interferon-gamma homologue by an intestinal nematode: functionally significant or interesting artefact? Parasitology 115: S101 S106.
39. Gurunathan, S.,, L. Stobie,, C. Prussin,, D. L. Sacks,, N. Glaichenhaus,, D. J. Fowell,, R. M. Locksley,, J. T. Chang,, C. Y. Wu,, and R. A. Seder. 2000. Requirements for the maintenance of Th1 immunity in vivo following DNA vaccination: a potential immunoregulatory role for CD8+ T cells. J. Immunol. 165: 915 924.
40. Helmby, H.,, K. Takeda,, S. Akira,, and R. K. Grencis. Interleukin (IL)-18 promotes the development of chronic gastrointestinal helminth infection by down-regulating IL-13. J. Exp. Med., in press.
41. Herndon, F. J.,, and S. G. Kayes. 1992. Depletion of eosinophils by anti-IL-5 monoclonal antibody treatment of mice infected with Trichinella spiralis does not alter parasite burden or immunologic resistance to reinfection. J. Immunol. 149: 3642 3647.
42. Holland, M. J.,, Y. M. Harcus,, P. L. Riches,, and R. M. Maizels. 2000. Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for Th2 responses. Eur. J. Immunol. 30: 1977 1987.
43. Holscher, C.,, G. Kohler,, U. Muller,, H. Mossmann,, G. A. Schaub,, and F. Brombacher. 1998. Defective nitric oxide effector functions lead to extreme susceptibility of Trypanosoma cruziinfected mice deficient in gamma interferon receptor or inducible nitric oxide synthase. Infect. Immun. 66: 1208 1215.
44. Huntley, J. F.,, C. Gooden,, G. F. Newlands,, A. Mackellar,, D. A. Lammas,, D. Wakelin,, M. Tuohy,, R. G. Woodbury,, and H. R. Miller. 1990. Distribution of intestinal mast cell proteinase in blood and tissues of normal and Trichinella-infected mice. Parasite Immunol. 12: 85 95.
45. Ing, R.,, Z. Su,, M. E. Scott,, and K. G. Koski. 2000. Suppressed T helper 2 immunity and prolonged survival of a nematode parasite in protein-malnourished mice. Proc. Natl. Acad. Sci. USA 97: 7078 7083.
46. Kamanaka, M.,, P. Yu,, T. Yasui,, K. Yoshida,, T. Kawabe,, T. Horii,, T. Kishimoto,, and H. Kikutani. 1996. Protective role of CD40 in Leishmania major infection at two distinct phases of cellmediated immunity. Immunity 4: 275 282.
47. Kang, H.,, J. S. Remington,, and Y. Suzuki. 2000. Decreased resistance of B cell-deficient mice to infection with Toxoplasma gondii despite unimpaired expression of IFN-gamma, TNF-alpha, and inducible nitric oxide synthase. J. Immunol. 164: 2629 2634.
48. Karlsson, N. G.,, F. J. Olson,, P. A. Jovall,, Y. Andersch,, L. Enerback,, and G. C. Hansson. 2000. Identification of transient glycosylation alterations of sialylated mucin oligosaccharides during infection by the rat intestinal parasite Nippostrongylus brasiliensis. Biochem. J. 350: 805 814.
49. Khan, I. A.,, T. Matsuura,, and L. H. Kasper. 1998. Inducible nitric oxide synthase is not required for long-term vaccine-based immunity against Toxoplasma gondii. J. Immunol. 161: 2994 3000.
50. Khan, W. I.,, T. Abe,, N. Ishikawa,, Y. Nawa,, and K. Yoshimura. 1995. Reduced amount of intestinal mucus by treatment with anti-CD4 antibody interferes with the spontaneous cure of Nippostrongylus brasiliensis infection in mice. Parasite Immunol. 17: 485 491.
51. Kima, P. E.,, S. L. Constant,, L. Hannum,, M. Colmenares,, K. S. Lee,, A. M. Haberman,, M. J. Shlomchik,, and D. McMahon- Pratt. 2000. Internalization of Leishmania mexicana complex amastigotes via the Fc receptor is required to sustain infection in murine cutaneous leishmaniasis. J. Exp. Med. 191: 1063 1068.
52. Kima, P. E.,, N. H. Ruddle,, and D. McMahon-Pratt. 1997. Presentation via the class I pathway by Leishmania amazonensisinfected macrophages of an endogenous leishmanial antigen to CD8+ T cells. J. Immunol. 159: 1828 1834.
53. Korenaga, M.,, T. Abe,, and Y. Hashiguchi. 1996. Injection of recombinant interleukin 3 hastens worm expulsion in mice infected with Trichinella spiralis. Parasitol. Res. 82: 108 113.
54. Korenaga, M.,, Y. Hitoshi,, K. Takatsu,, and I. Tada. 1994. Regulatory effect of anti-interleukin-5 monoclonal antibody on intestinal worm burden in a primary infection with strongyloides venezuelensis in mice. Int. J. Parasitol. 24: 951 957.
55. Koyama, K.,, H. Tamauchi,, M. Tomita,, T. Kitajima,, and Y. Ito. 1999. B-cell activation in the mesenteric lymph nodes of resistant BALB/ c mice infected with the murine nematode parasite Trichuris muris. Parasitol Res. 85: 194 199.
56. Kumar, S.,, and R. L. Tarleton. 1998. The relative contribution of antibody production and CD8+ T cell function to immune control of Trypanosoma cruzi. Parasite Immunol. 20: 207 216.
57. Lantz, C. S.,, J. Boesiger,, C. H. Song,, N. Mach,, T. Kobayashi,, R. C. Mulligan,, Y. Nawa,, G. Dranoff,, and S. J. Galli. 1998. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392: 90 93.
58. Lawrence, C. E.,, J. C. Paterson,, L. M. Higgins,, T. T. MacDonald,, M. W. Kennedy,, and P. Garside. 1998. IL-4-regulated enteropathy in an intestinal nematode infection. Eur. J. Immunol. 28: 2672 2684.
59. Lawrence, C. E.,, J. C. Paterson,, X. Q. Wei,, F. Y. Liew,, P. Garside,, and M. W. Kennedy. 2000. Nitric oxide mediates intestinal pathology but not immune expulsion during Trichinella spiralis infection in mice. J. Immunol. 164: 4229 4234.
60. Love, R. J.,, B. M. Ogilvie,, and D. J. McLaren. 1976. The immune mechanism which expels the intestinal stage of Trichinella spiralis from rats. Immunology 30: 7 15.
61. MacKenzie, C. R.,, R. Langen,, O. Takikawa,, and W. Daubener. 1999. Inhibition of indoleamine 2,3-dioxygenase in human macrophages inhibits interferon-gamma-induced bacteriostasis but does not abrogate toxoplasmastasis. Eur. J. Immunol. 29: 3254 3261.
62. Madden, K. B.,, J. F. Urban, Jr.,, H. J. Ziltener,, J. W. Schrader,, F. D. Finkelman,, and I. M. Katona. 1991. Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. J. Immunol. 147: 1387 1391.
63. McKenzie, G. J.,, P. G. Fallon,, C. L. Emson,, R. K. Grencis,, and A. N. McKenzie. 1999. Simultaneous disruption of interleukin (IL)-4 and IL-13 defines individual roles in T helper cell type 2- mediated responses. J. Exp. Med. 189: 1565 1572.
64. Medzhitov, R.,, and C. Janeway, Jr. 2000. Innate immune recognition: mechanisms and pathways. Immunol. Rev. 173: 89 97.
65. Mosmann, T. R.,, H. Cherwinski,, M. W. Bond,, M. A. Giedlin,, and R. L. Coffman. 1986. Two types of murine helper T cell clone. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 126: 2348 2357.
66. Muller, I.,, P. Kropf,, J. A. Louis,, and G. Milon. 1994. Expansion of gamma interferon-producing CD8+ T cells following secondary infection of mice immune to Leishmania major. Infect. Immun. 62: 2575 2581.
67. Murray, H. W.,, and C. F. Nathan. 1999. Macrophage microbicidal mechanisms in vivo: reactive nitrogen versus oxygen intermediates in the killing of intracellular visceral Leishmania donovani. J. Exp. Med. 189: 741 746.
68. Nashleanas, M.,, S. Kanaly,, and P. Scott. 1998. Control of Leishmania major infection in mice lacking TNF receptors. J. Immunol. 160: 5506 5513.
69. Pfefferkorn, E. R. 1984. Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc. Natl. Acad. Sci. USA 81: 908 912.
70. Prina, E.,, T. Lang,, N. Glaichenhaus,, and J. C. Antoine. 1996. Presentation of the protective parasite antigen LACK by Leishmania- infected macrophages. J. Immunol. 156: 4318 4327.
71. Pritchard, D. I.,, D. J. Williams,, J. M. Behnke,, and T. D. Lee. 1983. The role of IgG1 hypergammaglobulinaemia in immunity to the gastrointestinal nematode Nematospiroides dubius. The immunochemical purification, antigen-specificity and in vivo anti-parasite effect of IgG1 from immune serum. Immunology 49: 353 365.
72. Reed, S. G. 1998. Immunology of Trypanosoma cruzi infections. Chem. Immunol. 70: 124 143.
73. Richard, M.,, R. K. Grencis,, N. E. Humphreys,, J. C. Renauld,, and J. Van Snick. 2000. Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice. Proc. Natl. Acad. Sci. USA 97: 767 772.
74. Roach, T. I.,, K. J. Else,, D. Wakelin,, D. J. McLaren,, and R. K. Grencis. 1991. Trichuris muris: antigen recognition and transfer of immunity in mice by IgA monoclonal antibodies. Parasite Immunol. 13: 1 12.
75. Russell, D. G.,, E. Medina-Acosta,, and A. Golubev. 1991. The interface between the Leishmania-infected macrophage and the host’s immune system. Behring Inst. Mitt. 88: 68 79.
76. Sato, N.,, S. K. Ahuja,, M. Quinones,, V. Kostecki,, R. L. Reddick,, P. C. Melby,, W. A. Kuziel,, and S. S. Ahuja. 2000. CC chemokine receptor (CCR)2 is required for Langerhans cell migration and localization of T helper cell type 1 (Th1)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, B cell outgrowth, and sustained neutrophilic inflammation. J. Exp. Med. 192: 205 218.
77. Sayles, P. C.,, G. W. Gibson,, and L. L. Johnson. 2000. B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii. Infect. Immun. 68: 1026 1033.
78. Scharton-Kersten, T. M.,, G. Yap,, J. Magram,, and A. Sher. 1997. Inducible nitric oxide is essential for host control of persistent but not acute infection with the intracellular pathogen Toxoplasma gondii. J. Exp. Med. 185: 1261 1273.
79. Senn, K. A.,, K. D. McCoy,, K. J. Maloy,, G. Stark,, E. Frohli,, T. Rulicke,, and R. Klemenz. 2000. T1-deficient and T1-Fc-transgenic mice develop a normal protective Th2- type immune response following infection with Nippostrongylus brasiliensis. Eur. J. Immunol. 30: 1929 1938.
80. Solbach, W.,, and T. Laskay. 2000. The host response to Leishmania infection. Adv. Immunol. 74: 275 317.
81. Soong, L.,, J.-C. Su,, I. S. Grewal,, P. Kima,, J. Sun,, B. J. Longley,, N. H. Ruddle,, D. McMahon-Pratt,, and R. A. Flavell. 1996. Disruption of CD40-CD40 ligand interactions results in enhanced susceptibility to Leishmania amazonensis infection. Immunity 4: 263 274.
82. Sousa, C. R.,, S. Hieny,, T. Scharton-Kersten,, D. Jankovic,, H. Charest,, R. N. Germain,, and A. Sher. 1997. In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J. Exp. Med. 186: 1819 1829.
83. Sutterwala, F. S.,, G. J. Noel,, P. Salgame,, and D. M. Mosser. 1998. Reversal of proinflammatory responses by ligating the macrophage Fcgamma receptor type I. J. Exp. Med. 188: 217 222.
84. Taylor, A. P.,, and H. W. Murray. 1997. Intracellular antimicrobial activity in the absence of interferon-gamma: effect of interleukin- 12 in experimental visceral leishmaniasis in interferongamma gene-disrupted mice. J. Exp. Med. 185: 1231 1239.
85. Taylor, G. A.,, C. M. Collazo,, G. S. Yap,, K. Nguyen,, T. A. Gregorio,, L. S. Taylor,, B. Eagleson,, L. Secrest,, E. A. Southon,, S. W. Reid,, L. Tessarollo,, M. Bray,, D. W. McVicar,, K. L. Komschlies,, H. A. Young,, C. A. Biron,, A. Sher,, and G. F. Vande Woude. 2000. Pathogen-specific loss of host resistance in mice lacking the IFN-gamma-inducible gene IGTP. Proc. Natl. Acad. Sci. USA 97: 751 755.
86. Townsend, M. J.,, P. G. Fallon,, D. J. Matthews,, P. Smith,, H. E. Jolin,, and A. N. McKenzie . 2000 IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity 13: 573 583.
87. Trinchieri, G. 1998. Interleukin-12: a cytokine at the interface of inflammation and immunity. Adv. Immunol. 70: 83 243.
88. Uchikawa, R.,, S. Matsuda,, and N. Arizono. 2000. Suppression of gamma interferon transcription and production by nematode excretory-secretory antigen during polyclonal stimulation of rat lymph node T cells. Infect. Immun. 68: 6233 6239.
89. Urban, J. F., Jr.,, I. M. Katona,, W. E. Paul,, and F. D. Finkelman. 1991. Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc. Natl. Acad. Sci. USA 88: 5513 5517.
90. Urban, J. F., Jr.,, C. R. Maliszewski,, K. B. Madden,, I. M. Katona,, and F. D. Finkelman. 1995. IL-4 treatment can cure established gastrointestinal nematode infections in immunocompetent and immunodeficient mice. J. Immunol. 154: 4675 4684.
91. Urban, J. F., Jr.,, N. Noben-Trauth,, D. D. Donaldson,, K. B. Madden,, S. C. Morris,, M. Collins,, and F. D. Finkelman. 1998. IL- 13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity. 8: 255 264.
92. Urban, J. F., Jr.,, L. Schopf,, S. C. Morris,, T. Orekhova,, K. B. Madden,, C. J. Betts,, H. R. Gamble,, C. Byrd,, D. Donaldson,, K. Else,, and F. D. Finkelman 2000. Stat6 signaling promotes protective immunity against Trichinella spiralis through a mast celland T cell-dependent mechanism. J. Immunol. 164: 2046 2052.
93. Vallance, B. A.,, P. A. Blennerhassett,, and S. M. Collins. 1997. Increased intestinal muscle contractility and worm expulsion in nematode-infected mice. Am. J. Physiol. 272: G321 G327.
94. Vallance, B. A.,, K. Croitoru,, and S. M. Collins. 1998. T lymphocyte- dependent and -independent intestinal smooth muscle dysfunction in the T. spiralis-infected mouse. Am. J. Physiol. 275: G1157 G1165.
95. Vester, B.,, K. Muller,, W. Solbach,, and T. Laskay. 1999. Early gene expression of NK cell-activating chemokines in mice resistant to Leishmania major. Infect Immun. 67: 3155 3159.
96. Wakelin, D. 1978. Immunity to intestinal parasites. Nature 273: 617 620.
97. Wang, Z. E.,, S. L. Reiner,, F. Hatam,, F. P. Heinzel,, J. Bouvier,, C. W. Turck,, and R. M. Locksley. 1993. Targeted activation of CD8 cells and infection of beta-2-microglobulin-deficient mice fail to confirm a primary protective role for CD8 cells in experimental leishmaniasis. J. Immunol. 151: 2077 2086.
98. Wei, X.-Q.,, I. G. Charles,, A. Smith,, J. Ure,, G.-J. Feng,, F.-P. Huang,, X. Damo,, W. Muller,, S. Moncada,, and F. Y. Liew. 1995. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375: 408 411.
99. Weisbrodt, N. W.,, M. Lai,, R. L. Bowers,, Y. Harari,, and G. A. Castro. 1994. Structural and molecular changes in intestinal smooth muscle induced by Trichinella spiralis infection. Am. J. Physiol. 266: G856 G862.
100. Xu, D.,, V. Trajkovic,, D. Hunter,, B. P. Leung,, K. Schulz,, J. A. Gracie,, I. B. McInnes,, and F. Y. Liew. 2000. IL-18 induces the differentiation of Th1 or Th2 cells depending upon cytokine milieu and genetic background. Eur. J. Immunol. 30: 3147 3156.
101. Yap, G. S.,, T. Scharton-Kersten,, H. Charest,, and A. Sher. 1998. Decreased resistance of TNF receptor p55- and p75-deficient mice to chronic toxoplasmosis despite normal activation of inducible nitric oxide synthase in vivo. J. Immunol. 160: 1340 1345.
102. Yap, G. S.,, and A. Sher. 1999. Effector cells of both nonhemopoietic and hemopoietic origin are required for interferon (IFN)-gamma- and tumor necrosis factor (TNF)-alphadependent host resistance to the intracellular pathogen, Toxoplasma gondii. J. Exp. Med. 189: 1083 1092.
103. Yoshimoto, T.,, H. Mizutani,, H. Tsutsui,, N. Noben-Trauth,, K. Yamanaka,, M. Tanaka,, S. Izumi,, H. Okamura,, W. E. Paul,, and K. Nakanishi. 2000. IL-18 induction of IgE: dependence on CD4 T cells, IL-4 and STAT 6. Nat. Immunol. 1: 132 137.

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