Mice with STAT6-targeted gene disruption develop a Th1 response and control cutaneous leishmaniasis

Luisa M. Stamm, Anne Räisänen-Sokolowski, Mitsuhiro Okano, Mary E. Russell, John R. David, Abhay R. Satoskar

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Abstract

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.

Original languageEnglish
Pages (from-to)6180-6188
Number of pages9
JournalJournal of Immunology
Volume161
Issue number11
Publication statusPublished - Dec 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Stamm, L. M., Räisänen-Sokolowski, A., Okano, M., Russell, M. E., David, J. R., & Satoskar, A. R. (1998). Mice with STAT6-targeted gene disruption develop a Th1 response and control cutaneous leishmaniasis. Journal of Immunology, 161(11), 6180-6188.