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Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140
To determine the role of IL-10 in cutaneous leishmaniasis, we
examined lesion development following Leishmania major
infection of genetically susceptible BALB/c mice lacking IL-10. Whereas
normal BALB/c mice developed progressive nonhealing lesions with
numerous parasites within them, IL-10-/- BALB/c mice
controlled disease progression, and had relatively small lesions with
1000-fold fewer parasites within them by the fifth week of infection.
We also examined a mechanism whereby Leishmania induced
the production of IL-10 from macrophages. We show that surface IgG on
Leishmania amastigotes allows them to ligate Fc
receptors on inflammatory macrophages to preferentially induce the
production of high amounts of IL-10. The IL-10 produced by infected
macrophages prevented macrophage activation and diminished their
production of IL-12 and TNF-
. In vitro survival assays confirmed the
importance of IL-10 in preventing parasite killing by activated
macrophages. Pretreatment of monolayers with either rIL-10 or
supernatants from amastigote-infected macrophages resulted in a
dramatic enhancement in parasite intracellular survival. These studies
indicate that amastigotes of Leishmania use an unusual
and unexpected virulence factor, host IgG. This IgG allows amastigotes
to exploit the antiinflammatory effects of FcR ligation to induce
the production of IL-10, which renders macrophages refractory to the
activating effects of IFN-.
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P. Cameron, A. McGachy, M. Anderson, A. Paul, G. H. Coombs, J. C. Mottram, J. Alexander, and R. Plevin Inhibition of Lipopolysaccharide-Induced Macrophage IL-12 Production by Leishmania mexicana Amastigotes: The Role of Cysteine Peptidases and the NF-{kappa}B Signaling Pathway J. Immunol., September 1, 2004; 173(5): 3297 - 3304. [Abstract] [Full Text] [PDF]
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N. B. Norsworthy, J. Sun, D. Elnaiem, G. Lanzaro, and L. Soong Sand Fly Saliva Enhances Leishmania amazonensis Infection by Modulating Interleukin-10 Production Infect. Immun., March 1, 2004; 72(3): 1240 - 1247. [Abstract] [Full Text] [PDF]
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M. Hesse, C. A. Piccirillo, Y. Belkaid, J. Prufer, M. Mentink-Kane, M. Leusink, A. W. Cheever, E. M. Shevach, and T. A. Wynn The Pathogenesis of Schistosomiasis Is Controlled by Cooperating IL-10-Producing Innate Effector and Regulatory T Cells J. Immunol., March 1, 2004; 172(5): 3157 - 3166. [Abstract] [Full Text] [PDF]
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N. Noben-Trauth, R. Lira, H. Nagase, W. E. Paul, and D. L. Sacks The Relative Contribution of IL-4 Receptor Signaling and IL-10 to Susceptibility to Leishmania major J. Immunol., May 15, 2003; 170(10): 5152 - 5158. [Abstract] [Full Text] [PDF]
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D. V. R. Bullen, T. M. Baldwin, J. M. Curtis, W. S. Alexander, and E. Handman Persistence of Lesions in Suppressor of Cytokine Signaling-1-Deficient Mice Infected with Leishmania major J. Immunol., April 15, 2003; 170(8): 4267 - 4272. [Abstract] [Full Text] [PDF]
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M. Colmenares, S. L. Constant, P. E. Kima, and D. McMahon-Pratt Leishmania pifanoi Pathogenesis: Selective Lack of a Local Cutaneous Response in the Absence of Circulating Antibody Infect. Immun., December 1, 2002; 70(12): 6597 - 6605. [Abstract] [Full Text] [PDF]
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H. W. Murray, C. M. Lu, S. Mauze, S. Freeman, A. L. Moreira, G. Kaplan, and R. L. Coffman Interleukin-10 (IL-10) in Experimental Visceral Leishmaniasis and IL-10 Receptor Blockade as Immunotherapy Infect. Immun., November 1, 2002; 70(11): 6284 - 6293. [Abstract] [Full Text] [PDF]
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J. Li, U. M. Padigel, P. Scott, and J. P. Farrell Combined Treatment with Interleukin-12 and Indomethacin Promotes Increased Resistance in BALB/c Mice with Established Leishmania major Infections Infect. Immun., October 1, 2002; 70(10): 5715 - 5720. [Abstract] [Full Text] [PDF]
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 J. C. Delorenzi, L. Freire-de-Lima, C. R. Gattass, D. de Andrade Costa, L. He, M. E. Kuehne, and E. M. B. Saraiva In Vitro Activities of Iboga Alkaloid Congeners Coronaridine and 18-Methoxycoronaridine against Leishmania amazonensis Antimicrob. Agents Chemother., July 1, 2002; 46(7): 2111 - 2115. [Abstract] [Full Text] [PDF]
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P. Launois, A. Gumy, H. Himmelrich, R. M. Locksley, M. Rocken, and J. A. Louis Rapid IL-4 Production by Leishmania Homolog of Mammalian RACK1-Reactive CD4+ T Cells in Resistant Mice Treated Once with Anti-IL-12 or -IFN-{gamma} Antibodies at the Onset of Infection with Leishmania major Instructs Th2 Cell Development, Resulting in Nonhealing Lesions J. Immunol., May 1, 2002; 168(9): 4628 - 4635. [Abstract] [Full Text] [PDF]
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R. Lang, R. L. Rutschman, D. R. Greaves, and P. J. Murray Autocrine Deactivation of Macrophages in Transgenic Mice Constitutively Overexpressing IL-10 Under Control of the Human CD68 Promoter J. Immunol., April 1, 2002; 168(7): 3402 - 3411. [Abstract] [Full Text] [PDF]
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A. Sing, A. Roggenkamp, A. M. Geiger, and J. Heesemann Yersiniaenterocolitica Evasion of the Host Innate Immune Response by V Antigen-Induced IL-10 Production of Macrophages Is Abrogated in IL-10-Deficient Mice J. Immunol., February 1, 2002; 168(3): 1315 - 1321. [Abstract] [Full Text] [PDF]
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G. Trinchieri Regulatory Role of T Cells Producing both Interferon {gamma} and Interleukin 10 in Persistent Infection J. Exp. Med., November 19, 2001; 194(10): F53 - F57. [Full Text] [PDF]
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Y. Belkaid, K. F. Hoffmann, S. Mendez, S. Kamhawi, M. C. Udey, T. A. Wynn, and D. L. Sacks The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti-IL-10 Receptor Antibody for Sterile Cure J. Exp. Med., November 19, 2001; 194(10): 1497 - 1506. [Abstract] [Full Text] [PDF]
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