Persistence of lesions in suppressor of cytokine signaling-1-deficient mice infected with Leishmania major
- Author(s)
- Bullen, DVR; Baldwin, TM; Curtis, JM; Alexander, WS; Handman, E;
- Details
- Publication Year 2003-04-15,Volume 170,Issue #8,Page 4267-4272
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- To investigate the role of the cytokine IFN-gamma and its negative regulator, the suppressor of cytokine signaling-1 (SOCS1) in the progression of cutaneous leishmaniasis, we infected mice lacking a single copy of the gene encoding SOCS1 (SOCS1(+/-)), mice lacking both copies of IFN-gamma (IFN-gamma(-/-)), or mice lacking copies of both SOCS1 and IFN-gamma (SOCS1(-/-) IFN-gamma(-/-)), with a moderate dose of 10(3) or 10(4) of the most virulent stage of parasites, metacyclic promastigotes. Surprisingly, SOCS1(+/-) mice developed larger lesions than wild-type mice, although the parasite load in the draining lymph node was not significantly altered. These mice also developed apparently normal Th1 responses, as indicated by elevated levels of IFN-gamma and low levels of IL-4 and IL-10. The persistence of lesions and the enlargement of draining lymph nodes despite a normal Th1 response and control of parasitemia indicate that there may be a dissociation of the inflammatory pathology and clearance of parasites in SOCS1(+/-) mice. We also investigated the role of the related suppressor of cytokine signaling, SOCS2, which has been implicated in the development of Th1 immunity. The progression of disease in SOCS2(-/-) mice did not differ from that in C57BL/6 control mice, suggesting that it is not involved in the host response to Leishmania major infection and supporting the specific role of SOCS1. These results suggest that SOCS1 plays an important role in the regulation of appropriate inflammatory responses during the resolution of L major infection.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- INTERFERON-GAMMA; CUTANEOUS LEISHMANIASIS; LACKING SUPPRESSOR; NATURAL MODEL; IN-VIVO; INHIBITOR; DEGENERATION; PREVENTS; PROTEINS; DISEASE
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Creation Date: 2003-04-15 12:00:00