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Chapter 25 : Immune Evasion by Parasites
Authors:
John M. Mansfield1,
Martin Olivier2
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Affiliations:
1: Department of Bacteriology, University of Wisconsin—Madison, Madison, WI 53706;
2: Infectious Diseases Unit, CHUL, Laval University, Sainte-Foy, Quebec G1V 4G2, Canada
Content Type: Monograph
Publication Year:
2002
Category: Immunology
Book DOI:
10.1128/9781555817978
Chapter DOI:
10.1128/9781555817978.ch25
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Abstract:
This chapter examines two paradigms of parasite immune evasion during infection: one is a new theme emerging from a classic paradigm of surface antigen variation by extracellular parasites, and the other is a new paradigm of modified antigen recognition of intracellular parasites. A study was published with newer crystal structure data in a broader sequence survey of VSG molecules related by class (the pattern of Cys residues in the N terminus) and type (sequence similarities within the C terminus). The finding of the study was that the amino acid-hypervariable regions existed among different variant surface glycoprotein (VSG) and that some of these were buried within the surface coat. It was proposed that this represented evidence at the primary sequence level for antigenic variation within potential Th-cell epitope sites, and they made the formal hypothesis that antigenic variation by trypanosomes was done to evade host B- and T-cell responses. Additional evidence that VSG-specific Th-cell responses contribute to host resistance has come from a recent unexpected finding. In this work, C57BL/6-Igh-6 mice that lack mature B cells were infected with T. b. rhodesiense LouTat 1. Some parasites reside intracellularly during infection and do not exhibit substantial antigenic variation. In summary, the protozoan parasite Leishmania has developed several powerful strategies to subvert the macrophage signaling system, and this consequently affects the development of protective immune responses to favor parasite survival.
Citation:
Mansfield J, Olivier M.
2002.
Immune Evasion by Parasites,
p 379-392.
In
Kaufmann S, Sher A, Ahmed R (ed),
Immunology of Infectious Diseases.
ASM Press, Washington, DC.
doi: 10.1128/9781555817978.ch25
Key Concept Ranking
- Tumor Necrosis Factor alpha
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- Major Histocompatibility Complex
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- Immune Systems
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Figures
Immune Evasion by Parasites
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Citation:
Mansfield J, Olivier M.
2002.
Immune Evasion by Parasites,
p 379-392.
In
Kaufmann S, Sher A, Ahmed R (ed),
Immunology of Infectious Diseases.
ASM Press, Washington, DC.
doi: 10.1128/9781555817978.ch25
/content/10.1128/9781555817978.chap25.fig25-1
Figure 1
The trypanosome VSG coat presents a T-cell-independent surface “antigen pattern” that activates B cells. The three-dimensional or architectural array of exposed repetitive VSG epitopes is sufficient to activate B cells and produce a rapid immunoglobulin M response during infection in the absence of Th cells. Subsequent exposure of the immune system to VSG molecules liberated from the surface coat induces strong VSG-specific Th1-cell and T-dependent B-cell responses. Adapted from Mansfield (1994) .
10.1128/9781555817978/fig25-1_thmb.gif
10.1128/9781555817978/fig25-1.gif
Figure 1
The trypanosome VSG coat presents a T-cell-independent surface “antigen pattern” that activates B cells. The three-dimensional or architectural array of exposed repetitive VSG epitopes is sufficient to activate B cells and produce a rapid immunoglobulin M response during infection in the absence of Th cells. Subsequent exposure of the immune system to VSG molecules liberated from the surface coat induces strong VSG-specific Th1-cell and T-dependent B-cell responses. Adapted from Mansfield (1994) .
Citation:
Mansfield J, Olivier M.
2002.
Immune Evasion by Parasites,
p 379-392.
In
Kaufmann S, Sher A, Ahmed R (ed),
Immunology of Infectious Diseases.
ASM Press, Washington, DC.
doi: 10.1128/9781555817978.ch25
/content/10.1128/9781555817978.chap25.fig25-2
Figure 2
VSG molecules are members of a protein superfamily that exhibit a highly conserved structure. Two VSG molecules are shown that differ significantly in primary sequence but display conserved secondary and tertiary structural features; these structural features are retained among different molecules because VSGs contain highly conserved subsequences necessary for proper folding of the molecule. Highlighted in the figure are the minimal structural differences seen between these two VSGs, as well as other molecular landmarks ( Blum et al., 1993 ). Reprinted from Blum et al. (1993) with permission of the publisher.
10.1128/9781555817978/fig25-2_thmb.gif
10.1128/9781555817978/fig25-2.gif
Figure 2
VSG molecules are members of a protein superfamily that exhibit a highly conserved structure. Two VSG molecules are shown that differ significantly in primary sequence but display conserved secondary and tertiary structural features; these structural features are retained among different molecules because VSGs contain highly conserved subsequences necessary for proper folding of the molecule. Highlighted in the figure are the minimal structural differences seen between these two VSGs, as well as other molecular landmarks ( Blum et al., 1993 ). Reprinted from Blum et al. (1993) with permission of the publisher.
Citation:
Mansfield J, Olivier M.
2002.
Immune Evasion by Parasites,
p 379-392.
In
Kaufmann S, Sher A, Ahmed R (ed),
Immunology of Infectious Diseases.
ASM Press, Washington, DC.
doi: 10.1128/9781555817978.ch25
/content/10.1128/9781555817978.chap25.fig25-3
Figure 3
Th-cell-reactive sites are found within a buried hyper-variable region conserved among VSG molecules. The relative placement of three different hypervariable (HV) regions found within trypanosome VSGs is shown ( Field and Boothroyd, 1996 ). HV-2 and HV-3 are predicted to contain amino acids that would be exposed on the surface of the VSG coat, while HV-1 contains amino acids that are predicted to be buried within VSG molecules. The Th-cell-reactive subsequence shown for the LouTat 1 VSG lies within the predicted conserved HV-1 region.
10.1128/9781555817978/fig25-3_thmb.gif
10.1128/9781555817978/fig25-3.gif
Figure 3
Th-cell-reactive sites are found within a buried hyper-variable region conserved among VSG molecules. The relative placement of three different hypervariable (HV) regions found within trypanosome VSGs is shown ( Field and Boothroyd, 1996 ). HV-2 and HV-3 are predicted to contain amino acids that would be exposed on the surface of the VSG coat, while HV-1 contains amino acids that are predicted to be buried within VSG molecules. The Th-cell-reactive subsequence shown for the LouTat 1 VSG lies within the predicted conserved HV-1 region.
Citation:
Mansfield J, Olivier M.
2002.
Immune Evasion by Parasites,
p 379-392.
In
Kaufmann S, Sher A, Ahmed R (ed),
Immunology of Infectious Diseases.
ASM Press, Washington, DC.
doi: 10.1128/9781555817978.ch25
/content/10.1128/9781555817978.chap25.fig25-4
Figure 4
Induction of host cell phosphatases by L. donovani infection. The Ca2+-dependent serine / threonine phosphatase PP-2B (calcineurin) activity is increased over the Ser /Thr phosphatase PP- 1 and P-2A activities in Leishmania-infected macrophages. PTP activity is rapidly triggered by Leishmania, and, in particular, the PTP SHP-1 is recognized for its role as a negative signaling regulator in leukocytes.
10.1128/9781555817978/fig25-4_thmb.gif
10.1128/9781555817978/fig25-4.gif
Figure 4
Induction of host cell phosphatases by L. donovani infection. The Ca2+-dependent serine / threonine phosphatase PP-2B (calcineurin) activity is increased over the Ser /Thr phosphatase PP- 1 and P-2A activities in Leishmania-infected macrophages. PTP activity is rapidly triggered by Leishmania, and, in particular, the PTP SHP-1 is recognized for its role as a negative signaling regulator in leukocytes.
Citation:
Mansfield J, Olivier M.
2002.
Immune Evasion by Parasites,
p 379-392.
In
Kaufmann S, Sher A, Ahmed R (ed),
Immunology of Infectious Diseases.
ASM Press, Washington, DC.
doi: 10.1128/9781555817978.ch25
References
/content/book/10.1128/9781555817978.chap25
1.
Allred, D. R. 1998. Antigenic variation in Babesia bovis: how similar is it to that in Plasmodium falciparum? Ann. Trop. Med. Parasitol. 92: 461– 472.
2.
Anderson, R. M. 1998. Complex dynamic behaviours in the interaction between parasite population and the host’s immune system. Int. J. Parasitol. 28: 551– 566.
3.
Bachmann, M. F.,, and R. Zinkernagel. 1996. The influence of virus structure on antibody responses and virus serotype formation. Immunol. Today 17: 553– 558.
4.
Belosevic, M.,, D. S. Findbloom,, M. S. Meltzer,, and C. A. Nacy. 1990. IL-2. A cofactor for induction of activated macrophage resistance to infection. J. Immunol. 145: 831– 839.
5.
Berger, S.,, R. Chandra,, H. Ballo,, R. Hildenbrand,, and H. J. Stutte. 1997. Immune complexes are potent inhibitors of interleukin- 12 secretion by human monocytes. Eur. J. Immunol. 27: 2994– 3000.
6.
Blanchette, J.,, N. Racette,, K. A. Siminovitch,, R. Faure,, and M. Olivier. 1999. Leishmania-induced increases in activation of macrophage SHP-1 phosphatase are associated with impaired IFN-γ-triggered JAK2 activation. Eur. J. Immunol. 29: 3737– 3744.
7.
Bliska, J. B.,, J. E. Galan,, and S. Falkow. 1993. Signal transduction in the mammalian cell during bacterial attachment and entry. Cell 73: 903– 920.
8.
Bliska, J. B.,, K. L. Guan,, J. E. Dixon,, and S. Falkow. 1991. Tyrosine phosphate hydrolysis of host proteins by an essential Yersinia virulence determinant. Proc. Natl. Acad. Sci. USA 88: 1187– 1191.
9.
Blum, J. L.,, J. A. Down,, A. M. Gurnett,, M. Carrington,, M. J. Turner,, and D. C. Wiley. 1993. A structural motif in the variant surface glycoproteins of Trypanosoma brucei. Nature 362: 603– 609.
10.
Borst, P.,, and G. A. Cross. 1982. Molecular basis for trypanosome antigenic variation. Cell 29: 291– 303.
11.
Borst, P.,, A. C. Frasch,, A. Bernards,, L. H. Van der Ploeg,, J. H. Hoeijmakers,, A. C. Arnberg,, and G. A. Cross. 1981. DNA rearrangements involving the genes for variant antigens in Trypanosoma brucei. Cold Spring Harbor Symp. Quant. Biol. 2: 935– 943.
12.
Borst, P.,, and G. Rudenko. 1994. Antigenic variation in African trypanosomes. Science 264: 1872– 1873.
13.
Borst, P.,, G. Rudenko,, M. C. Taylor,, P. A. Blundell,, F. Vanleeuwen,, W. Bitter,, M. Cross,, and R. McCulloch. 1996. Antigenic variation In trypanosomes. Arch. Med. Res. 27: 379– 388.
14.
Brown, M. G.,, J. Driscoll,, and J. J. Monaco. 1991. Structural and serological similarity of MHC-linked LMP and proteasome (multicatalytic proteinase) complexes. Nature 353: 355– 357.
15.
Carrington, M.,, N. Miller,, M. Blum,, I. Roditi,, D. Wiley,, and M. Turner. 1991. Variant specific glycoprotein of Trypanosoma brucei consists of two domains each having an independently conserved pattern of cysteine residues J. Mol. Biol. 221: 823– 835.
16.
Chaussepied, M.,, D. Lallemand,, M. F. Moreau,, R. Adamson,, R. Hall,, and G. Langsley. 1998. Upregulation of Jun and Fos family members and permanent JNK activity lead to constitutive AP- 1 activation in Theileria-transformed leukocytes. Mol. Biochem. Parasitol. 94: 215– 226.
17.
Chen, Z.,, J. Hagler,, V. J. Palombella,, F. Melandri,, D. Scherer,, D. Ballard,, and T. Maniatis. 1995. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev. 9: 1586– 1597.
18.
Cross, G. 1990. Cellular and genetic aspects of antigenic variation in trypanosomes. Annu. Rev. Immunol. 8: 83– 110.
19.
Cross, G. A. 1975. Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei. Parasitology 71: 393– 417.
20.
Cross, G. A. 1996. Antigenic variation in trypanosomes: secrets surface slowly. Bioessays 18: 283– 291.
21.
Cross, G. A.,, L. E. Wirtz,, and M. Navarro. 1998. Regulation of vsg expression site transcription and switching in Trypanosoma brucei Mol. Biochem. Parasitol. 91: 77– 91.
22.
Damian, R. T. 1997. Parasite immune evasion and exploitation: reflections and projections. Parasitology 115: S169– S175.
23.
Darnell, J. E. 1997. STATs and gene regulation. Science 277: 1630– 1635.
24.
Dea-Ayuela, M. A.,, and F. Bolas-Fernandez. 1999. Trichinella antigens: a review. Vet. Res. 30: 559– 571.
25.
De Gee, A. L.,, R. F. Levine,, and J. M. Mansfield. 1988. Genetics of resistance to the African trypanosomes. VI. Heredity of resistance and variable surface glycoprotein-specific immune responses. J. Immunol. 140: 283– 288.
26.
De Gee, A. L.,, and J. M. Mansfield. 1984. Genetics of resistance to the African trypanosomes. IV. Resistance of radiation chimeras to Trypanosoma rhodesiense infection. Cell. Immunol. 87: 85– 91.
27.
De Gee, A. L.,, G. Sonnenfeld,, and J. M. Mansfield. 1985. Genetics of resistance to the African trypanosomes. V. Qualitative and quantitative differences in interferon production among susceptible and resistant mouse strains. J. Immunol. 134: 2723– 2726.
28.
Dominguez, M.,, and A. Torano. 1999. Immune adherence-mediated opsonophagocytosis: the mechanism of Leishmania infection. J. Exp. Med. 189: 25– 35.
29.
Donelson, J. E.,, K. L. Hill,, and N. M. El-Sayed. 1998. Multiple mechanisms of immune evasion by African trypanosomes. Mol. Biochem. Parasitol. 91: 51– 66.
30.
Dong, Z.,, C. A. O’Brian,, and I. J. Fidler. 1993a. Activation of tumoricidal properties in macrophages by lipopolysaccharide requires protein-tyrosine kinase activity. J. Leukoc. Biol. 53: 53– 60.
31.
Dong, Z.,, X. Qi,, K. Xie,, and I. J. Fidler. 1993b. Protein tyrosine kinase inhibitors decrease induction of nitric oxide synthase activity in lipopolysaccharide-responsive and lipopolysaccharide-nonresponsive murine macrophages. J. Immunol. 151: 2717– 2724.
32.
Fantl, W. J.,, D. E. Johnson,, and L. T. Williams. 1993. Signalling by receptor tyrosine kinases. Annu. Rev. Biochem. 62: 453– 481.
33.
Fearon, D. T.,, and R. M. Locksley. 1996. The instructive role of innate immunity in the acquired immune response. Science 272: 50– 53.
34.
Field, M. C.,, and J. C. Boothroyd. 1996. Sequence divergence in a family of variant surface glycoprotein genes from trypanosomes: coding region hypervariability and downstream recombinogenic repeats. J. Mol. Evol. 42: 500– 511.
35.
Glaser, K. B.,, A. Sung,, J. Bauer,, and B. M. Weichman. 1993. Regulation of eicosanoid biosynthesis in the macrophage. Involvement of protein tyrosine phosphorylation and modulation by selective protein tyrosine kinase inhibitors. Biochem. Pharmacol. 45: 711– 721.
36.
Golden, A.,, and J. S. Brugge. 1989. Thrombin treatment induces rapid changes in tyrosine phosphorylation in platelets. Proc. Natl. Acad. Sci. USA 86: 901– 905.
37.
Golden, A.,, S. P. Nemeth,, and J. S. Brugge. 1986. Blood platelets express high levels of the pp60c-src-specific tyrosine kinase activity. Proc. Natl. Acad. Sci. USA 83: 852– 856.
38.
Green, S. P.,, J. A. Hamilton,, and W. A. Phillips. 1992. Zymosan-triggered tyrosine phosphorylation in mouse bone-marrow-derived macrophages is enhanced by respiratory-burst priming agents. Biochem. J. 288: 427– 432.
39.
Greenberg, S.,, P. Chang,, and S. C. Silverstein. 1993. Tyrosine phosphorylation of the gamma subunit of Fc gamma receptors, p72syk, and paxillin during Fc receptor-mediated phagocytosis in macrophages. J. Biol. Chem. 269: 3897– 3902.
40.
Guy, R. A.,, and M. Belosevic. 1993. Comparison of receptors required for entry of Leishmania major amastigotes into macrophages. Infect. Immun. 61: 1553– 1558.
41.
Haque, S.,, H. Dumon,, A. Haque,, and L. H. Kasper. 1998. Alteration of intracellular calcium flux and impairment of nuclear factor-AT translocation in T cells during acute Toxoplasma gondii infection in mice. J. Immunol. 161: 6812– 6818.
42.
Harnett, W.,, M. R. Deehan,, K. M. Houston,, and M. M. Harnett. 1999. Immunomodulatory properties of a phosphorylcholine containing secreted filarial glycoprotein. Parasite Immunol. 21: 601– 608.
43.
Haspel, R. L. M. Salditt-Georgieff, and J. E. Darnell. 1996. The rapid inactivation of nuclear tyrosine phosphorylated Stat1 depends upon a protein tyrosine phosphatase. EMBO J. 15: 6262– 6268.
44.
Heinzel, F. P.,, M. D. Sadick,, B. J. Holaday,, R. L. Coffman,, and R. M. Locksley. 1989. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J. Exp. Med. 169: 59– 72.
45.
Heinzel, F. P.,, M. D. Sadick,, and R. M. Locksley. 1988. Leishmania major: analysis of lymphocyte and macrophage cellular phenotypes during infection of susceptible and resistant mice. Exp. Parasitol. 65: 258– 268.
46.
Hertz, C. J.,, and J. M. Mansfield. 1999. IFN-gamma-dependent nitric oxide production is not linked to resistance in experimental African trypanosomiasis. Cell. Immunol. 192: 24– 32.
47.
Hertz, C. J.,, H. Filutowicz,, and J. M. Mansfield. 1998. Resistance to the African trypanosomes is IFN-gamma dependent. J. Immunol. 161: 6775– 6783.
48.
Hoeijmakers, J. H.,, A. C. Frasch,, A. Bernards,, P. Borst,, and G. A. Cross. 1980. Novel expression-linked copies of the genes for variant surface antigens in trypanosomes. Nature 284: 78– 80.
49.
Hommel, M. 1997. Modulation of host cell receptors: a mechanism for the survival of malaria parasites. Parasitology 115: S45– S54.
50.
Hooft van Huijsduijnen, R. 1998. Protein tyrosine phosphatases: counting the trees in the forest. Gene 225: 1– 8.
51.
Horn, D.,, and G. A. Cross. 1997. Analysis of Trypanosoma brucei vsg expression site switching in vitro. Mol. Biochem. Parasitol. 84: 189– 201.
52.
Hunter, T. 1993. Signal transduction. Cytokine connections. Nature 366: 114– 116.
53.
Hunter, T.,, and B. M. Sefton. 1980. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc. Natl. Acad. Sci. USA 77: 1311– 1315.
54.
Hunter, T.,, and J. A. Cooper. 1985. Protein-tyrosine kinases. Annu. Rev. Biochem. 54: 897– 930.
55.
Kima, P. E.,, N. H. Ruddle,, and D. McMahon-Pratt. 1987. Presentation via the class I pathway by Leishmania amazonensis infected macrophages of an endogenous leishmanial antigen to CD8+ T cells. J. Immunol. 159: 1828– 1834.>
56.
Klee, C. B.,, T. H. Crouch,, and M. H. Krinks. 1979. Calcineurin: a calcium- and calmodulin-binding protein of the nervous system. Proc. Natl. Acad. Sci. USA 76: 6270– 6273.
57.
Kozlowski, M.,, I. Mlinaric-Rascan,, G. S. Feng,, R. Shen,, T. Pawson,, and K. A. Siminovitch. 1993. Expression and catalytic activity of the tyrosine phosphatase PTP1C is severely impaired in motheaten and viable motheaten mice. J. Exp. Med. 178: 2157– 2163.
58.
Kukita, M.,, M. Hirata,, and T. Koga. 1986. Requirement of Ca2+ for the production and degradation of inositol 1,4,5- triphosphate in macrophages. Biochim. Biophys. Acta 885: 121– 128.
59.
Leonard, W. J.,, and J. J. O’Shea. 1998. JAKs and STATs: biological implications. Annu. Rev. Immunol. 16: 293– 322.
60.
Liu, B.,, J. Liao,, X. Rao,, S. A. Kushner,, C. D. Chung,, D. D. Chang,, and K. Shuai. 1998. Inhibition of Stat1-mediated gene activation by PIAS1. Proc. Natl. Acad. Sci. USA 95: 10626– 10631.
61.
Locksley, R. M.,, F. P. Heinzel,, B. J. Holaday,, S. S. Mutha,, S. L. Reiner,, and M. D. Sadick. 1991. Induction of Th1 and Th2 CD4+ subsets during murine Leishmania major infection. Res. Immunol. 142: 28– 32.
62.
Locksley, R. M.,, F. P. Heinzel,, M. D. Sadick,, B. J. Holaday,, and K. Gardner. 1987. Murine cutaneous leishmaniasis: susceptibility correlates with differential expansion of helper T-cell subsets. Ann. Inst. Pasteur Immunol. 138: 744– 749.
63.
Locksley, R. M.,, and P. Scott. 1991. Helper T-cell subsets in mouse leishmaniasis: induction, expansion and effector function. Immunol. Today 12: A58– A61.
64.
Locksley, R. M.,, A. E. Wakil,, D. B. Corry,, S. Pingel,, M. Bix,, and D. J. Fowell. 1995. The development of effector T cell subsets in murine Leishmania major infection. Ciba Found. Symp. 195: 110– 117.
65.
Mansfield, J. M. 1994. T-cell responses to the trypanosome variant surface glycoprotein: a new paradigm? Parasitol. Today 10: 267– 270.>
66.
Mansfield, J. M., 1995. Immunobiology of African trypanosomiasis: a revisionist view, p. 477– 496. In J. C. Boothroyd, and R. Komuniecki (ed.), Molecular Approaches to Parasitology. Wiley- Liss, New York, N.Y..
67.
Mansfield, J. M.,, R. F. Levine,, W. L. Dempsey,, S. R. Wellhausen,, and C. T. Hansen. 1981. Lymphocyte function in experimental African trypanosomiasis. IV. Immunosuppression and suppressor cells in the athymic nu/nu mouse. Cell. Immunol. 63: 210– 215.
68.
Marth, T.,, and B. L. Kelsall. 1997. Regulation of interleukin-12 by complement receptor 3 signaling. J. Exp. Med. 185: 1987– 1995.
69.
Matte, C.,, J.-F. Marquis,, J. Blanchette,, P. Gros,, R. Faure,, and M. Olivier. 2000. Peroxovanadium-mediated protection against murine leishmaniasis: role of the modulation of nitric oxide. Eur. J. Immunol. 30: 2555– 2564.
70.
Matthews, R. J.,, D. B. Bowne,, E. Flores,, and M. L. Thomas. 1992. Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences. Mol. Cell. Biol. 12: 2396– 2405.
71.
Mauel, J. 1990. Macrophage-parasite interactions in Leishmania infections. J. Leukoc. Biol. 47: 187– 193.
72.
Metcalf, P.,, M. Blum,, D. Freymann,, M. Turner,, and D. C. Wiley. 1987. Two variant surface glycoproteins of Trypanosoma brucei of different sequence classes have similar 6 Å resolution X-ray structures Nature 325: 84– 86.
73.
Mosser, D. M.,, and P. J. Edelson. 1984. Activation of the alternative complement pathway by Leishmania promastigotes: parasite lysis and attachment to macrophages. J. Immunol. 132: 1501– 1505.
74.
Mosser, D. M.,, and P. J. Edelson. 1985. The mouse macrophage receptor for C3bi (CR3) is a major mechanism in the phagocytosis of Leishmania promastigotes. J. Immunol. 135: 2785– 2789.
75.
Moudgil, K. D.,, E. E. Sercarz,, and I. S. Grewal. 1998. Modulation of the immunogenicity of antigenic determinants by their flanking residues. Immunol. Today 19: 217– 220.
76.
Muller, M.,, J. Briscoe,, C. Laxton,, D. Guschin,, A. Ziemiecki,, O. Silvennoinen,, A. G. Harpur,, G. Barbieri,, B. A. Witthuhn,, C. Schindler, et al. 1993. The protein tyrosine kinase JAK1 complements defects in interferon-alpha / beta and -gamma signal transduction. Nature 366: 129– 135.
77.
Muller, N.,, and B. Gottstein. 1998. Antigenic variation and the murine immune response to Giardia lamblia. Int. J. Parasitol. 28: 1829– 1839.
78.
Murray, H. W.,, H. Masur,, and J. S. Keithly. 1982. Cell-mediated immune response in experimental visceral leishmaniasis. I. Correlation between resistance to Leishmania donovani and lymphokine- generating capacity. J. Immunol. 129: 344– 350.
79.
Murray, H. W.,, J. J. Stern,, K. Welte,, B. Y. Rubin,, S. M. Carriero,, and C. F. Nathan. 1987. Experimental visceral leishmaniasis: production of interleukin 2 and interferon-gamma, tissue im mune reaction, and response to treatment with interleukin 2 and interferon-gamma. J. Immunol. 138: 2290– 2297.
80.
Nash, T. E. 1997. Antigenic variation in Giardia lamblia and the host’s immune response. Philos. Trans. R. Soc. London Ser. B 352: 1369– 1375.
81.
Navarro, M.,, and G. A. M. Cross. 1996. DNA rearrangements associated with multiple consecutive directed antigenic switches in Trypanosoma brucei. Mol. Cell. Biol. 16: 3615– 3625.
82.
Newbold, C. I. 1999. Antigenic variation in Plasmodium falciparum: mechanisms and consequences. Curr. Opin. Microbiol. 2: 420– 425.
83.
Olivier, M. 1996. Modulation of host cell intracellular Ca 2+. Parasitol. Today 12: 145– 150.
84.
Olivier, M.,, K. G. Baimbridge,, and N. E. Reiner. 1992a. Stimulus-response coupling in monocytes infected with Leishmania. Attenuation of calcium transients is related to defective agonist-induced accumulation of inositol phosphates. J. Immunol. 148: 1188– 1196.
85.
Olivier, M.,, S. Bertrand,, and C. E. Tanner. 1989a. Killing of Leishmania donovani by activated liver macrophages from resistant and susceptible strains mice. Int. J. Parasitol. 19: 377– 383.
86.
Olivier, M.,, R. W. Brownsey,, and N. E. Reiner. 1992b. Defective stimulus-response coupling in human monocytes infected with Leishmania donovani is associated with altered activation and translocation of protein kinase C. Proc. Natl. Acad. Sci. USA 89: 7481– 7485.
87.
Olivier, M.,, C. Proulx,, and C. E. Tanner. 1989b. Importance of lymphokines in the control of the multiplication and dispersion of Leishmania donovani within liver macrophages of resistant and susceptible mice. J. Parasitol. 75: 720– 727.
88.
Olivier, M.,, B. J. Romero-Gallo,, C. Matte,, J. Blanchette,, B. I. Posner,, M. J. Tremblay,, and R. Faure. 1998. Modulation of interferon-gamma-induced macrophage activation by phosphotyrosine phosphatases inhibition. Effect on murine leishmaniasis progression. J. Biol. Chem. 273: 13944– 13949.
89.
Olivier, M.,, and C. Tanner,. 1989. The effect of cyclosporin A in murine visceral leishmaniasis. Trop. Med. Parasitol. 40: 32– 38. Plutzky, J.,, B. B. Neel,, and R. D. Rosenberg. 1992. Isolation of a src homology 2-containing tyrosine phosphatase. Proc. Natl. Acad. Sci. USA 89: 1123– 1127.
90.
Posner, B. I.,, R. Faure,, J. W. Burgess,, A. P. Bevan,, D. Lachance,, G. Zhang-Sun,, J. B. Ng,, D. A. Hall,, B. S. Lum,, and A. Shaver. 1994. Peroxovanadium compounds. A new class of potent phosphotyrosine phosphatase inhibitors which are insulin mimetics. J. Biol. Chem. 269: 4596– 4604.
91.
Ramasamy, R. 1998. Molecular basis for evasion of host immunity and pathogenesis in malaria. Biochim. Biophys. Acta 1406: 10– 27.
92.
Ray, M.,, A. A. Gam,, R. A. Boykins,, and R. T. Kenney. 2000. Inhibition of interferon-γ signaling by Leishmania donovani. J. Infect. Dis. 181: 1121– 1128.
93.
Reiner, N. E.,, W. Ng,, T. Ma,, and W. R. McMaster. 1988. Kinetics of gamma interferon binding and induction of major histocompatibility complex class II mRNA in Leishmania-infected macrophages. Proc. Natl. Acad. Sci. USA 85: 4330– 4334.
94.
Reiner, N. E.,, W. Ng,, and W. R. McMaster. 1987. Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products. J. Immunol. 138: 1926– 1932.
95.
Reiner, S. L.,, and R. M. Locksley. 1995. The regulation of immunity to Leishmania major. Ann. Rev. Immunol. 13: 151– 177.
96.
Reinitz, D. M.,, B. D. Aizenstein,, and J. M. Mansfield. 1992. Variable and conserved structural elements of trypanosome variant surface glycoproteins. Mol. Biochem. Parasitol. 51: 119– 132.
97.
Reinitz, D. M.,, and J. M. Mansfield. 1988. Independent regulation of B cell responses to surface and subsurface epitopes of African trypanosome variable surface glycoproteins. J. Immunol. 141: 620– 626.
98.
Reinitz, D. M.,, and J. M. Mansfield. 1990. T-cell-independent and T-cell-dependent B-cell responses to exposed variant surface glycoprotein epitopes in trypanosome-infected mice. Infect. Immun. 58: 2337– 2342.
99.
Rivett, A. J. 1998. Intracellular distribution of proteasomes. Curr. Opin. Immunol. 10: 110– 114.
100.
Roach, P. J. 1991. Multisite and hierarchal protein phosphorylation. J. Biol. Chem. 266: 14139– 14142.
101.
Russell, D. G.,, and P. Talamas-Rohana. 1989. Leishmania and the macrophage: a marriage of inconvenience. Immunol. Today 10: 328– 333.
102.
Scharton-Kersten, T.,, and P. Scott. 1995. The role of the innate immune response in Th1 cell development following Leishmania major infection. J. Leukoc. Biol. 57: 515– 522.
103.
Schleifer, K. W.,, H. Filutowicz,, L. R. Schopf,, and J. M. Mansfield. 1993. Characterization of T helper cell responses to the trypanosome variant surface glycoprotein. J. Immunol. 150: 2910– 2919.
104.
Schleifer, K. W.,, and J. M. Mansfield. 1993. Suppressor macrophages in African trypanosomiasis inhibit T cell proliferative responses by nitric oxide and prostaglandins. J. Immunol. 151: 5492– 5503.
105.
Schneider, S. C.,, and E. E. Sercarz. 1997. Antigen processing differences among APC. Hum. Immunol. 54: 148– 158.
106.
Schopf, L. R.,, H. Filutowicz,, X. J. Bi,, and J. M. Mansfield. 1998. Interleukin-4-dependent immunoglobulin G1 isotype switch in the presence of a polarized antigen-specific Th1-cell response to the trypanosome variant surface glycoprotein Infect. Immun. 66: 451– 461.
107.
Schopf, L. R.,, and J. M. Mansfield. 1998. Characterization of a relatively rare class B, type 2 trypanosome variant surface glycoprotein gene. J. Parasitol. 84: 284.
108.
Schwarzer, E.,, M. Alessio,, D. Ulliers,, and P. Arese. 1998. Phagocytosis of the malarial pigment, hemozoin, impairs expression of major histocompatibility complex class II antigen, CD54, and CD11c in human monocytes. Infect. Immun. 66: 1601– 1606.
109.
Schwarzer, E.,, and P. Arese. 1996. Phagocytosis of malarial pigment hemozoin inhibits NADPH-oxidase activity in human monocyte-derived macrophages. Biochim. Biophys. Acta 1316: 169– 175.
110.
Scott, P. 1990. T-cell subsets and T-cell antigens in protective immunity against experimental leishmaniasis. Curr. Top. Microbiol. Immunol. 155: 35– 52.
111.
Scott, P. 1991. Host and parasite factors regulating the development of CD4+ T-cell subsets in experimental cutaneous leishmaniasis. Res. Immunol. 142: 32– 36.
112.
Scott, P.,, E. Pearce,, A. W. Cheever,, R. L. Coffman,, and A. Sher. 1989. Role of cytokines and CD4+ T-cell subsets in the regulation of parasite immunity and disease. Immunol. Rev. 112: 161– 182.
113.
Seed, J. R.,, and J. B. Sechelski. 1989. African trypanosomes: inheritance of factors involved in resistance. Exp. Parasitol. 69: 1– 8.
114.
Sercarz, E. E. 1998. Immune focusing vs diversification and their connection to immune regulation. Immunol. Rev. 164: 5– 10.
115.
Shen, S.-H.,, L. Bastien,, B. I. Posner,, and P. Chretien. 1991. A protein-tyrosine phosphatase with sequence similarity to the SH2 domain of the protein-tyrosine kinases. Nature 352: 736– 739.
116.
Shuai, K.,, G. R. Stark,, I. M. Kerr,, and J. E. Darnell. 1993. A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science 261: 1744– 1746.
117.
Silvennoinen, O.,, J. N. Ihle,, J. Schlessinger,, and D. E. Levy. 1993. Interferon-induced nuclear signalling by Jak protein tyrosine kinases. Nature 366: 583– 585.
118.
Snapper, C. M.,, M. R. Kehry,, B. E. Castle,, and J. J. Mond. 1995a. Multivalent, but not divalent, antigen receptor cross-linkers synergize with CD40 ligand for induction of Ig synthesis and class switching in normal murine B cells. A redefinition of the TI-2 vs T cell-dependent antigen dichotomy J. Immunol. 154: 1177– 1187.
119.
Snapper, C. M., and J. J. Mond. 1996. A model for induction of T cell-independent humoral immunity in response to polysaccharide antigens. J. Immunol. 157: 2229– 2233.
120.
Snapper, C. M.,, F. R. Rosas,, L. Jin,, C. Wortham,, M. R. Kehry,, and J. J. Mond. 1995b. Bacterial lipoproteins may substitute for cytokines in the humoral immune response to T cell-independent type II antigens. J. Immunol. 155: 5582– 5589.
121.
Snapper, C. M.,, H. Yamaguchi,, M. A. Moorman,, and J. J. Mond. 1994. An in vitro model for T cell-independent induction of humoral immunity. A requirement for NK cells. J. Immunol. 152: 4884– 4892.
122.
Stenger, S.,, N. Donhauser,, H. Thüring,, M. Röllinghoff,, and C. Bogdan. 1996. Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase. J. Exp. Med. 183: 1501– 1514.
123.
Stohwasser, R.,, S. Standera,, I. Peters,, P. M. Kloetzel,, and M. Groettrup. 1997. Molecular cloning of the mouse proteasome subunits MC14 and MECL-1: reciprocally regulated tissue expression of interferon-gamma-modulated proteasome subunits. Eur. J. Immunol. 27: 1182– 1187.
124.
Sutterwala, F. S.,, G. J. Noel,, R. Clynes,, and D. M. Mosser. 1997. Selective suppression of interleukin-12 induction after macrophage receptor ligation. J. Exp. Med. 185: 1977– 1985..
125.
Tachado, S. D.,, P. Gerold,, R. Schwarz,, S. Novakovic,, M. Mc- Conville,, and L. Schofield. 1997. Signal transduction in macrophages by glycosylphosphatidylinositols of Plasmodium, Trypanosoma, and Leishmania: activation of protein tyrosine kinases and protein kinase C by inositolglycan and diacylglycerol moieties. Proc. Natl. Acad. Sci. USA 94: 4022– 4027.
126.
Tachado, S. D.,, R. Mazhari-Tabrizi,, and L. Schofield. 1999. Specificity in signal transduction among glycosylphosphatidylinositols of Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. Parasite Immunol. 21: 609– 617.
127.
Turco, S. J. 1999. Adversarial relationship between the leishmania lipophosphoglycan and protein kinase C of host macrophages. Parasite Immunol. 21: 597– 600.
128.
Turner, C. M.,, and J. D. Barry. 1989. High frequency of antigenic variation in Trypanosoma brucei rhodesiense infections. Parasitology 1: 67– 75.
129.
Turner, C. M. R. 1997. The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei. FEMS Microbiol. Lett. 153: 227– 231.
130.
Van der Ploeg, L. H.,, K. Gottesdiener,, and M. G. Lee. 1992. Antigenic variation in African trypanosomes. Trends Genet. 8: 452– 457.
131.
Vickerman, K.,, and A. G. Luckins. 1969. Localization of variable antigens in the surface coat of Trypanosoma brucei using ferritin conjugated antibody. Nature 224: 1125– 1126.
132.
Walton, K. M.,, and J. E. Dixon. 1993. Protein tyrosine phosphatases. Annu. Rev. Biochem. 62: 101– 120.
133.
Watling, D.,, D. Guschin,, M. Muller,, O. Silvennoinen,, B. A. Witthuhn,, F. W. Quelle,, N. C. Rogers,, C. Schindler,, G. R. Stark,, J. N. Ihle, et al. 1993. Complementation by the protein tyrosine kinase JAK2 of a mutant cell line defective in the interferon-gamma signal transduction pathway. Nature 366: 166– 170.
134.
Yeung, Y. G.,, K. L. Berg,, F. J. Pixley,, R. H. Angeletti,, and E. R. Stanley. 1992. Protein tyrosine phosphatase-1C is rapidly phosphorylated in tyrosine in macrophages in response to colony stimulating factor-1. J. Biol. Chem. 267: 23447– 23450.
135.
Yi, T.,, J. L. Cleveland,, and J. N. Ihle. 1992. Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13. Mol. Cell. Biol. 12: 836– 846.
136.
Yu, C. L.,, and S. J. Burakoff. 1997. Involvement of proteasomes in regulating Jak-STAT pathways upon interleukin-2 stimulation. J. Biol. Chem. 272: 14017– 14020.
137.
Zinkernagel, R. M. 2000. What is missing in immunology to understand immunity? Nat. Immunol. 1: 181– 185.