Control of New World cutaneous leishmaniasis is IL‐12 independent but STAT4 dependent

Leishmania mexicana, a New World protozoan parasite, induces small, chronic, but non‐progressive lesions in C57BL/6 (B6) mice. In this study we investigated the role of IL‐12, and subsequent Th1 factors, in controlling cutaneous L. mexicana infection. IL‐12 treatment failed to promote disease resolu...

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Veröffentlicht in:European journal of immunology 2002-11, Vol.32 (11), p.3206-3215
Hauptverfasser: Buxbaum, Laurence U., Uzonna, Jude E., Goldschmidt, Michael H., Scott, Phillip
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Sprache:eng
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Zusammenfassung:Leishmania mexicana, a New World protozoan parasite, induces small, chronic, but non‐progressive lesions in C57BL/6 (B6) mice. In this study we investigated the role of IL‐12, and subsequent Th1 factors, in controlling cutaneous L. mexicana infection. IL‐12 treatment failed to promote disease resolution, suggesting that the inability of mice to heal is not related to a deficiency of endogenous IL‐12 production. Surprisingly, L. mexicana‐induced cutaneous lesions in wild‐type and IL‐12p40‐deficient mice were indistinguishable, with similar parasite burdens, immune responses, and lesion histopathology. In contrast, iNOS, IFN‐γ, and STAT4‐deficient mice developed progressive disease and uncontrolled parasite growth. These results differ dramatically from L. major infection, in which IL‐12p40‐deficient mice are highly susceptible, with very rapid lesion growth, very large parasite burdens, and the development of a strong Th2 response.These data uncover the existence of an alternate IFN‐γ and iNOS pathway for control of Leishmania lesions, which is IL‐12 independent, but which unexpectedly requires STAT4.
ISSN:0014-2980
1521-4141
DOI:10.1002/1521-4141(200211)32:11<3206::AID-IMMU3206>3.0.CO;2-J