Chapter 35 : Suppression of Immune Responses to Protozoan Parasites

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This chapter focuses on three protozoan parasites: malaria, , and , that have in common their transmission by insect vectors, their intracellular lifestyle in the mammalian host, and the requirement for Th1 responses to control these infections. It discusses the mechanisms used by these parasites to actively suppress the development and/or expression of cell-mediated immunity that contribute to the state of equilibrium that is established between the host and the parasite in sites of chronic infection. The chapter describes the manner in which protozoan pathogens have learned to condition their initial encounter with dendritic cells (DCs) as a means to suppress or delay the onset of the adaptive response. Infection with parasites typically produces an acute blood and tissue parasitemia that is controlled, followed by long-term persistence of low numbers of parasites in muscle and nerve tissue, leading to chronic inflammation in these tissues and the formation of Chagas’ disease. In leishmaniasis, there has been a concerted effort to understand the immunologic defects controlling both the delayed onset of acquired resistance and the long-term persistence of organisms in the immune host following clinical cure. The chapter talks about a number of regulatory T-cell populations that have in common their ability to suppress the generation and function of effector T cells. For , its ability to infect any nucleated cell type and to subsequently escape from endocytic vacuoles, allows it to persist in cell types and in an intracellular compartment that minimizes exposure to the toxic metabolites of activated cells.

Citation: Sacks D. 2011. Suppression of Immune Responses to Protozoan Parasites, p 441-451. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch35
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Subsets of regulatory and IL-10 producing T cells implicated in the suppression of immune responses to protozoan pathogens. nTregs undergo selection in the thymus for relatively high affinity recognition of self-peptide/MHC (major histocompatibility complexes). Their expansion in response to parasitic infection can be due to parasite antigens bearing cross-reactive epitopes with the self, or to activation of self-reactive clones in inflammatory sites rich in IL-2 and activated DCs. In most experimental and clinical studies in which the expansion of Foxp3 Treg cells have been described, it is not possible to distinguish their origin from iTregs, which are generated following an encounter of conventional T cells with antigen in the periphery and in response to high levels of TGF-β. The presence of iTregs in patients with malaria is inferred from antigen specificity and correlation with elevated serum concentrations of TGF-β. Tr1 cells are peripherally differentiated IL-10Foxp3CD4 T cells generated in response to antigen presented by regulatory DCs, which typically express subimmunogenic levels of antigen-MHC and costimulatory molecules, and secrete IL-10. IL-10 Th1 cells are T-betIFN-γ effector cells that simultaneously secrete IL-10. Their development can be driven by high dose or persistent antigen and IL-12 or IL-27.

Citation: Sacks D. 2011. Suppression of Immune Responses to Protozoan Parasites, p 441-451. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch35
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Image of FIGURE 2

Negative feedback loop initiated by protozoan pathogens inducing strong Th1 responses. TLR agonists and other stimulatory molecules delivered to DCs by malaria-infected RBCs (red blood cells), trypomastigotes or amastigotes, during the acute stage of infection, activate Th1 effector cells that, under the influence of persistent, high dose antigen and instruction by IL-12 or IL-27, will comprise a population of cells that are transiently activated to coexpress IL-10. The IL-10 from Th1 cells will down regulate APC (antigen-presenting cell) function and, in conjunction with reduced antigen available for processing during the immune clearance phase, will establish conditions suitable for the predominance of a regulatory DC phenotype and activation of Tr1 cells that help to limit the effector response during the chronic stage of infection.

Citation: Sacks D. 2011. Suppression of Immune Responses to Protozoan Parasites, p 441-451. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch35
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1. Accapezzato, D.,, V. Francavilla,, M. Paroli,, M. Casciaro,, L. V. Chircu,, A. Cividini,, S. Abrignani,, M. U. Mondelli, and, V. Barnaba. 2004. Hepatic expansion of a virus-specific regulatory CD8(+) T cell population in chronic hepatitis C virus infection. J. Clin. Invest. 113: 963972.
2. Amante,, F. H.,, A. C. Stanley,, L. M. Randall,, Y. Zhou,, A. Haque,, K. McSweeney,, A. P. Waters,, C. J. Janse,, M. F. Good,, G. R. Hill, and, C. R. Engwerda. 2007. A role for natural regulatory T cells in the pathogenesis of experimental cerebral malaria. Am. J. Pathol. 171: 548559.
3. Anderson, C. F.,, M. Oukka,, V. J. Kuchroo, and, D. Sacks. 2007. CD4(+)CD25(-)Foxp3(-) Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J. Exp. Med. 204: 285297.
4. Anderson,, C. F.,, J. S. Stumhofer,, C. A. Hunter, and, D. Sacks. 2009. IL-27 regulates IL-10 and IL-17 from CD4 + cells in nonhealing Leishmania major infection. J. Immunol. 183: 46194627.
5. Araujo,, F. F.,, J. A. Gomes,, M. O. Rocha,, S. Williams-Blangero,, V. M. Pinheiro,, M. J. Morato, and, R. Correa-Oliveira. 2007. Potential role of CD4+CD25HIGH regulatory T cells in morbidity in Chagas’ disease. Front Biosci. 12: 27972806.
6. Belkaid, Y.,, C. A. Piccirillo,, S. Mendez,, E. M. Shevach, and, D. L. Sacks. 2002. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420: 502507.
7. Bourreau, E.,, C. Ronet,, E. Darcissac,, M. C. Lise,, D. Sainte Marie,, E. Clity,, F. Tacchini-Cottier,, P. Couppie, and, P. Launois. 2009. Intralesional regulatory T-cell suppressive function during human acute and chronic cutaneous leishmaniasis due to Leishmania guyanensis. Infect. Immun. 77: 14651474.
8. Brodskyn,, C., J. Patricio,, R. Oliveira,, L. Lobo,, A. Arnholdt,, L. Mendonca-Previato,, A. Barral, and, M. Barral-Netto. 2002. Glycoinositolphospholipids from Trypanosoma cruzi interfere with macrophages and dendritic cell responses. Infect. Immun. 70: 37363743.
9. Campanelli,, A. P.,, A. M. Roselino,, K. A. Cavassani,, M. S. Pereira,, R. A. Mortara,, C. I. Brodskyn,, H. S. Goncalves,, Y. Belkaid,, M. Barral-Netto,, A. Barral, and, J. S. Silva. 2006. CD4+CD25+ T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells. J. Infect. Dis. 193: 13131322.
10. Costa,, G. C.,, M. O. da Costa Rocha,, P. R. Moreira,, C. A. Menezes,, M. R. Silva,, K. J. Gollob, and, W. O. Dutra. 2009. Functional IL-10 gene polymorphism is associated with Chagas’ disease cardiomyopathy. J. Infect. Dis. 199: 451454.
11. Couper,, K. N.,, D. G. Blount,, M. S. Wilson,, J. C. Hafalla,, Y. Belkaid,, M. Kamanaka,, R. A. Flavell,, J. B. de Souza, and, E. M. Riley. 2008. IL-10 from CD4CD25Foxp3CD127 adaptive regulatory T cells modulates parasite clearance and pathology during malaria infection. PLoS Pathog. 4: e1000004.
12. Cuellar,, A.,, S. P. Santander,, C. Thomas Mdel,, F. Guzman,, A. Gomez,, M. C. Lopez, and, C. J. Puerta. 2008. Monocytederived dendritic cells from chagasic patients vs healthy donors secrete differential levels of IL-10 and IL-12 when stimulated with a protein fragment of Trypanosoma cruzi heat-shock protein-70. Immunol. Cell Biol. 86: 255260.
13. Dutra, W. O.,, M. O. Rocha, and, M. M. Teixeira. 2005. The clinical immunology of human Chagas’ disease. Trends Parasitol. 21: 581587.
14. Elliott,, S. R.,, T. P. Spurck,, J. M. Dodin,, A. G. Maier,, T. S. Voss,, F. Yosaatmadja,, P. D. Payne,, G. I. McFadden,, A. F. Cowman,, S. J. Rogerson,, L. Schofield, and, G. V. Brown. 2007. Inhibition of dendritic cell maturation by malaria is dose dependent and does not require Plasmodium falciparum erythrocyte membrane protein 1. Infect. Immun. 75: 36213632.
15. Finney,, O. C.,, D. Nwakanma,, D. J. Conway,, M. Walther, and, E. M. Riley. 2009. Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmission. Eur. J. Immunol. 39: 12881300.
16. Freire-de-Lima,, C. G.,, D. O. Nascimento,, M. B. Soares,, P. T. Bozza,, H. C. Castro-Faria-Neto,, F. G. de Mello,, G. A. DosReis, and, M. F. Lopes. 2000. Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages. Nature 403: 199203.
17. Gazzinelli, R. T., and, E. Y. Denkers. 2006. Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism. Nat. Rev. Immunol. 6: 895906.
18. Golgher, D., and, R. T. Gazzinelli. 2004. Innate and acquired immunity in the pathogenesis of Chagas’ disease. Autoimmunity 37: 399409.
19. Gomes-Silva, A.,, R. de Cassia Bittar,, R. Dos Santos Nogueira,, V. S. Amato,, M. da Silva Mattos,, M. P. Oliveira-Neto,, S. G. Coutinho, and, A. M. Da-Cruz. 2007. Can interferongamma and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection? Clin. Exp. Immunol. 149: 440444.
20. Hisaeda, H.,, Y. Maekawa,, D. Iwakawa,, H. Okada,, K. Himeno,, K. Kishihara,, S. Tsukumo, and, K. Yasutomo. 2004. Escape of malaria parasites from host immunity requires CD4(+) CD25(+) regulatory T cells. Nat. Med. 10: 2930.
21. Hunter,, C. A.,, L. A. Ellis-Neyes,, T. Slifer,, S. Kanaly,, G. Grunig,, M. Fort,, D. Rennick, and, F. G. Araujo. 1997. IL-10 is required to prevent immune hyperactivity during infection with Trypanosoma cruzi. J. Immunol. 158: 33113316.
22. Jankovic,, D.,, M. C. Kullberg,, C. G. Feng,, R. S. Goldszmid,, C. M. Collazo,, M. Wilson,, T. A. Wynn,, M. Kamanaka,, R. A. Flavell, and, A. Sher. 2007. Conventional T-bet(+) Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J. Exp. Med. 204: 273283.
23. Jankovic,, D.,, M. C. Kullberg,, S. Hieny,, P. Caspar,, C. M. Collazo, and, A. Sher. 2002. In the absence of IL-12, CD4(+) T cell responses to intracellular pathogens fail to default to a Th2 pattern and are host protective in an IL-10(—/—) setting. Immunity 16: 429439.
24. Kossodo, S.,, C. Monso,, P. Juillard,, T. Velu,, M. Goldman, and, G. E. Grau. 1997. Interleukin-10 modulates susceptibility in experimental cerebral malaria. Immunology 91: 536540.
25. Kotner, J., and, R. Tarleton. 2007. Endogenous CD4+CD25 + regulatory T cells have limited role in control of Trypanosoma cruzi infection in mice. Infect Immun. 861869. doi:10.1128/IAI.01500-06
26. Lahl, K.,, C. Loddenkemper,, C. Drouin,, J. Freyer,, J. Arnason,, G. Eberl,, A. Hamann,, H. Wagner,, J. Huehn, and, T. Sparwasser. 2007. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J. Exp. Med. 204: 5763.
27. Liu, D.,, C. Kebaier,, N. Pakpour,, A. A. Capul,, S. M. Beverley,, P. Scott, and, J. E. Uzonna. 2009. Leishmania major phosphoglycans influence the host early immune response by modulating dendritic cell functions. Infect. Immun. 77: 32723283.
28. Mariano,, F. S.,, F. R. Gutierrez,, W. R. Pavanelli,, C. M. Milanezi,, K. A. Cavassani,, A. P. Moreira,, B. R. Ferreira,, F. Q. Cunha,, C. R. Cardoso, and, J. S. Silva. 2008. The involvement of CD4+CD25+ T cells in the acute phase of Trypanosoma cruzi infection. Microbes Infect. 10: 825833.
29. McDowell,, M. A.,, M. Marovich,, R. Lira,, M. Braun, and, D. Sacks. 2002. Leishmania priming of human dendritic cells for CD40 ligand-induced interleukin-12p70 secretion is strain and species dependent. Infect. Immun. 70: 39944001.
30. McGuirk, P.,, C. McCann, and, K. H. Mills. 2002. Pathogenspecific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis. J. Exp. Med. 195: 221231.
31. Melby,, P. C.,, F. J. Andrade-Narvaez,, B. J. Darnell,, G. Valencia-Pacheco,, V. V. Tryon, and, A. Palomo-Cetina. 1994. Increased expression of proinflammatory cytokines in chronic lesions of human cutaneous leishmaniasis. Infect. Immun. 62: 837842.
32. Michailowsky,, V.,, M. R. Celes,, A. P. Marino,, A. A. Silva,, L. Q. Vieira,, M. A. Rossi,, R. T. Gazzinelli,, J. Lannes-Vieira, and, J. S. Silva. 2004. Intercellular adhesion molecule 1 deficiency leads to impaired recruitment of T lymphocytes and enhanced host susceptibility to infection with Trypanosoma cruzi. J. Immunol. 173: 463470.
33. Millington,, O. R.,, C. Di Lorenzo,, R. S. Phillips,, P. Garside, and, J. M. Brewer. 2006. Suppression of adaptive immunity to heterologous antigens during Plasmodium infection through hemozoin-induced failure of dendritic cell function. J. Biol. 5: 5.
34. Murray,, H. W.,, C. M. Lu,, S. Mauze,, S. Freeman,, A. L. Moreira,, G. Kaplan, and, R. L. Coffman. 2002. Interleukin-10 (IL-10) in experimental visceral leishmaniasis and IL-10 receptor blockade as immunotherapy. Infect. Immunity 70: 62846293.
35. Nylen, S.,, R. Maurya,, L. Eidsmo,, K. D. Manandhar,, S. Sundar, and, D. Sacks. 2007. Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis. J. Exp. Med. 204: 805817.
36. O’Garra, A.,, P. L. Vieira,, P. Vieira, and, A. E. Goldfeld. 2004. IL-10-producing and naturally occurring CD4+ Tregs: limiting collateral damage. J. Clin. Invest. 114: 13721378.
37. Omer, F. M.,, J. B. de Souza, and, E. M. Riley. 2003. Differential induction of TGF-beta regulates proinflammatory cytokine production and determines the outcome of lethal and nonlethal Plasmodium yoelii infections. J. Immunol. 171: 54305436.
38. Perry,, J. A.,, C. S. Olver,, R. C. Burnett, and, A. C. Avery. 2005. Cutting edge: the acquisition of TLR tolerance during malaria infection impacts T cell activation. J. Immunol. 174: 59215925.
39. Poncini,, C. V.,, C. D. Alba Soto,, E. Batalla,, M. E. Solana, and, S. M. Gonzalez Cappa. 2008. Trypanosoma cruzi induces regulatory dendritic cells in vitro. Infect. Immun. 76: 26332641.
40. Ranatunga,, D.,, C. M. Hedrich,, F. Wang,, D. W. McVicar,, N. Nowak,, T. Joshi,, L. Feigenbaum,, L. R. Grant,, S. Stager, and, J. H. Bream. 2009. A human IL10 BAC transgene reveals tissue-specific control of IL-10 expression and alters disease outcome. Proc. Natl. Acad. Sci. USA 106: 1712317128.
41. Riley, E. M.,, S. Wahl,, D. J. Perkins, and, L. Schofield. 2006. Regulating immunity to malaria. Parasite Immunol. 28: 3549.
42. Rutz, S.,, M. Janke,, N. Kassner,, T. Hohnstein,, M. Krueger, and, A. Scheffold. 2008. Notch regulates IL-10 production by T helper 1 cells. Proc. Natl. Acad. Sci. USA 105: 34973502.
43. Sacks, D., and, C. Anderson. 2004. Re-examination of the immunosuppressive mechanisms mediating non-cure of Leishmania infection in mice. Immunol. Rev. 201: 225238.
44. Sacks, D., and, A. Sher. 2002. Evasion of innate immunity by parasitic protozoa. Nat. Immunol. 3: 10411047.
45. Sales,, P. A., Jr.,, D. Golgher,, R. V. Oliveira,, V. Vieira,, R. M. Arantes,, J. Lannes-Vieira, and, R. T. Gazzinelli. 2008. The regulatory CD4+CD25+ T cells have a limited role on pathogenesis of infection with Trypanosoma cruzi. Microbes Infect. 10: 680688.
46. Salhi, A.,, V. Rodrigues, Jr.,, F. Santoro,, H. Dessein,, A. Romano,, L. R. Castellano,, M. Sertorio,, S. Rafati,, C. Chevillard,, A. Prata,, A. Alcais,, L. Argiro, and, A. Dessein. 2008. Immunological and genetic evidence for a crucial role of IL-10 in cutaneous lesions in humans infected with Leishmania braziliensis. J., Immunol. 180: 61396148.
47. Saraiva,, M.,, J. R. Christensen,, M. Veldhoen,, T. L. Murphy,, K. M. Murphy, and, A. O’Garra. 2009. Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity 31: 209219.
48. Shaw,, M. H.,, G. J. Freeman,, M. F. Scott,, B. A. Fox,, D. J. Bzik,, Y. Belkaid, and, G. S. Yap. 2006. Tyk2 negatively regulates adaptive Th1 immunity by mediating IL-10 signaling and promoting IFN-gamma-dependent IL-10 reactivation. J. Immunol. 176: 72637271.
49. Skorokhod,, O. A.,, M. Alessio,, B. Mordmuller,, P. Arese, and, E. Schwarzer. 2004. Hemozoin (malarial pigment) inhibits differentiation and maturation of human monocyte-derived dendritic cells: a peroxisome proliferator-activated receptorgammamediated effect. J. Immunol. 173: 40664074.
50. Soong, L. 2008. Modulation of dendritic cell function by Leishmania parasites. J. Immunol. 180: 43554360.
51. Souza,, P. E.,, M. O. Rocha,, E. Rocha-Vieira,, C. A. Menezes,, A. C. Chaves,, K. J. Gollob, and, W. O. Dutra. 2004. Monocytes from patients with indeterminate and cardiac forms of Chagas’ disease display distinct phenotypic and functional characteristics associated with morbidity. Infect. Immun. 72: 52835291.
52. Sponaas,, A. M.,, E. T. Cadman,, C. Voisine,, V. Harrison,, A. Boonstra,, A. O’Garra, and, J. Langhorne. 2006. Malaria infection changes the ability of splenic dendritic cell populations to stimulate antigen-specific T cells. J. Exp. Med. 203: 14271433.
53. Stager, S.,, A. Maroof,, S. Zubairi,, S. L. Sanos,, M. Kopf, and, P. M. Kaye. 2006. Distinct roles for IL-6 and IL-12p40 in mediating protection against Leishmania donovani and the expansion of IL-10+ CD4+ T cells. Eur. J. Immunol. 36: 17641771.
54. Steeg, C.,, G. Adler,, T. Sparwasser,, B. Fleischer, and, T. Jacobs. 2009. Limited role of CD4+Foxp3+ regulatory T cells in the control of experimental cerebral malaria. J. Immunol. 183: 70147022.
55. Stumhofer, J. S., and, C. A. Hunter. 2008. Advances in understanding the anti-inflammatory properties of IL-27. Immunol. Lett. 117: 123130.
56. Suffia,, I. J.,, S. K. Reckling,, C. A. Piccirillo,, R. S. Goldszmid, and, Y. Belkaid. 2006. Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens. J. Exp. Med. 203: 777788.
57. Svensson, M.,, A. Maroof,, M. Ato, and, P. M. Kaye. 2004. Stromal cells direct local differentiation of regulatory dendritic cells. Immunity 21: 805816.
58. Torcia,, M. G.,, V. Santarlasci,, L. Cosmi,, A. Clemente,, L. Maggi,, V. D. Mangano,, F. Verra,, G. Bancone,, I. Nebie,, B. S. Sirima,, F. Liotta,, F. Frosali,, R. Angeli,, C. Severini,, A. R. Sannella,, P. Bonini,, M. Lucibello,, E. Maggi,, E. Garaci,, M. Coluzzi,, F. Cozzolino,, F. Annunziato,, S. Romagnani, and, D. Modiano. 2008. Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria. Proc. Natl. Acad. Sci. USA 105: 646651.
59. Trinchieri, G. 2001. Regulatory role of T cells producing both interferon gamma and interleukin 10 in persistent infection. J. Exp. Med. 194: F53F57.
60. Urban, B.,, N. Willcox, and, D. Roberts. 2001. A role for CD36 in the regulation of dendritic cell function. Proc. Natl. Acad. Sci. USA 98: 87508755.
61. Urban,, B. C.,, D. Cordery,, M. J. Shafi,, P. C. Bull,, C. I. Newbold,, T. N. Williams, and, K. Marsh. 2006. The frequency of BDCA3-positive dendritic cells is increased in the peripheral circulation of Kenyan children with severe malaria. Infect. Immun. 74: 67006706.
62. Van Overtvelt, L.,, N. Vanderheyde,, V. Verhasselt,, J. Ismaili,, L. De Vos,, M. Goldman,, F. Willems, and, B. Vray. 1999. Trypanosoma cruzi infects human dendritic cells and prevents their maturation: inhibition of cytokines, HLA-DR, and costimulatory molecules. Infect. Immun. 67: 40334040.
63. Vigario,, A. M.,, O. Gorgette,, H. C. Dujardin,, T. Cruz,, P. A. Cazenave,, A. Six,, A. Bandeira, and, S. Pied. 2007. Regulatory CD4+ CD25+ Foxp3+ T cells expand during experimental Plasmodium infection but do not prevent cerebral malaria. Int. J. Parasitol. 37: 963973.
64. Vitelli-Avelar,, D. M.,, R. Sathler-Avelar,, J. C. Dias,, V. P. Pascoal,, A. Teixeira-Carvalho,, P. S. Lage,, S. M. Eloi-Santos,, R. Correa-Oliveira, and, O. A. Martins-Filho. 2005. Chagasic patients with indeterminate clinical form of the disease have high frequencies of circulating CD3+′″ CD16-CD56+ natural killer T cells and CD4+CD25High regulatory T lymphocytes. Scand. J. Immunol. 62: 297308.
65. Waghabi,, M. C.,, M. Keramidas,, J. J. Feige,, T. C. Araujo-Jorge, and, S. Bailly. 2005. Activation of transforming growth factor beta by Trypanosoma cruzi. Cell. Microbiol. 7: 511517.
66. Wakkach, A.,, N. Fournier,, V. Brun,, J. P. Breittmayer,, F. Cottrez, and, H. Groux. 2003. Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18: 605617.
67. Walther, M.,, D. Jeffries,, O. C. Finney,, M. Njie,, A. Ebonyi,, S. Deininger,, E. Lawrence,, A. Ngwa-Amambua,, S. Jayasooriya,, I. H. Cheeseman,, N. Gomez-Escobar,, J. Okebe,, D. J. Conway, and, E. M. Riley. 2009. Distinct roles for FOXP3 and FOXP3 CD4 + T cells in regulating cellular immunity to uncomplicated and severe Plasmodium falciparum malaria. PLoS Pathog. 5: e1000364.
68. Walther,, M.,, J. E. Tongren,, L. Andrews,, D. Korbel,, E. King,, H. Fletcher,, R. F. Andersen,, P. Bejon,, F. Thompson,, S. J. Dunachie,, F. Edele,, J. B. de Souza,, R. E. Sinden,, S. C. Gilbert,, E. M. Riley, and, A. V. Hill. 2005. Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity 23: 287296.
69. Wanasen, N.,, L. Xin, and, L. Soong. 2008. Pathogenic role of B cells and antibodies in murine Leishmania amazonensis infection. Int. J. Parasitol. 38: 417429.
70. Wong, K. A., and, A. Rodriguez. 2008. Plasmodium infection and endotoxic shock induce the expansion of regulatory dendritic cells. J. Immunol. 180: 716726.
71. Wykes,, M. N.,, X. Q. Liu,, L. Beattie,, D. I. Stanisic,, K. J. Stacey,, M. J. Smyth,, R. Thomas, and, M. F. Good. 2007. Plasmodium strain determines dendritic cell function essential for survival from malaria. PLoS Pathog. 3: e96.
72. Xin, L.,, K. Li, and, L. Soong. 2008. Down-regulation of dendritic cell signaling pathways by Leishmania amazonensis amastigotes. Mol Immunol 45: 33713382.
73. Yamazaki, S., and, R. M. Steinman. 2009. Dendritic cells as controllers of antigen-specific Foxp3+ regulatory T cells. J. Dermatol. Sci. 54: 6975.
74. Zhang, L., and, R. L. Tarleton. 1999. Parasite persistence correlates with disease severity and localization in chronic Chagas’ disease. J. Infect. Dis. 180: 480486.


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Dendric cell (DC) functional defects induced by protozoan pathogens

Citation: Sacks D. 2011. Suppression of Immune Responses to Protozoan Parasites, p 441-451. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch35

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