The cutaneous growth of Leishmania mexicana was measured in STAT6- deficient mice (STAT6(-/-)) and compared with that in similarly infected wild-type (STAT6(+/+)) mice. Following s.c. inoculation with 5 x 106 amastigotes of L. mexicana into the shaven rump, STAT6(+/+) mice developed large, nonhealing cutaneous lesions, while STAT6(-/-) mice failed to develop detectable lesions during most of the course of study. As infection progressed, STAT6(+/+) mice infected with L. mexicana displayed significantly higher titers of Leishmania-specific IgG1 and IgE compared with STAT6(-/-) mice, which conversely produced significantly higher titers of Leishmania- specific IgG2a, indicating development of a Th1-like response in the latter group. At 12 wk postinfection, Leishmania Ag-stimulated lymph node cells from STAT6(-/-) mice produced significantly higher amounts of IL-12 and IFN-γ than those from STAT6(+/+) mice as measured by ELISA. However, there was no significant difference in IL-4 production between the two groups. Semiquantitative RT-PCR of transcript levels in intact draining lymph nodes and skin from inoculation sites confirmed a similar pattern of cytokines in vivo as that observed in stimulated lymph node cells in vitro. These results indicate that STAT6-mediated IL-4 signaling is critical for progression of L. mexicana infection in genetically susceptible mice and demonstrate that in the absence of STAT6, susceptible mice default toward a Th1-like response and control cutaneous L. mexicana infection.
|Number of pages||9|
|Journal||Journal of Immunology|
|Publication status||Published - Dec 1 1998|
ASJC Scopus subject areas
- Immunology and Allergy