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Media type:
E-Article
Title:
Anti-TGF-β Treatment Promotes Rapid Healing ofLeishmania majorInfection in Mice by Enhancing In Vivo Nitric Oxide Production
Contributor:
Li, Jian;
Hunter, Christopher A.;
Farrell, Jay P.
Published:
The American Association of Immunologists, 1999
Published in:
The Journal of Immunology, 162 (1999) 2, Seite 974-979
Language:
English
DOI:
10.4049/jimmunol.162.2.974
ISSN:
0022-1767;
1550-6606
Origination:
Footnote:
Description:
AbstractCB6F1 mice display intermediate susceptibility to Leishmania major infection compared with the highly susceptible BALB/c and resistant C57BL/6 parental strains. During early weeks of infection, these mice develop dominant Th2 type responses to L. major, although they eventually exhibit a Th2 to Th1 switch and spontaneously resolve their infections. In this study, we have examined the effects of either IL-12 or anti-TGF-β therapy on the immune response and course of disease in chronically infected CB6F1 mice. Local treatment with IL-12 inoculated into the parasitized lesion at 4 wk of infection induced a marked increase in IFN-γ production but did not result in a significant reduction in numbers of parasite or promote more rapid healing. However, local treatment with an Ab to TGF-β led to both a decrease in parasite numbers and more rapid healing, despite the fact that such treatment did not significantly alter the pattern of IL-4 and IFN-γ production. Immunohistochemical studies showed that anti-TGF-β treatment resulted in increased nitric oxide production within parasitized lesions. Our results suggest that TGF-β may play an important regulatory role during chronic stages of a L. major infection by suppressing macrophage production of nitric oxide and that, in the absence of TGF-β, even the relatively low levels of IFN-γ observed in mice with dominant Th2-type responses are sufficient to activate macrophages to destroy amastigotes within parasitized lesions.