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 language | English |
|---|---|
| Pages (from-to) | 6180-6188 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 161 |
| Issue number | 11 |
| Publication status | Published - Dec 1 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Mice with STAT6-targeted gene disruption develop a Th1 response and control cutaneous leishmaniasis. / Stamm, Luisa M.; Räisänen-Sokolowski, Anne; Okano, Mitsuhiro; Russell, Mary E.; David, John R.; Satoskar, Abhay R.
In: Journal of Immunology, Vol. 161, No. 11, 01.12.1998, p. 6180-6188.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mice with STAT6-targeted gene disruption develop a Th1 response and control cutaneous leishmaniasis
AU - Stamm, Luisa M.
AU - Räisänen-Sokolowski, Anne
AU - Okano, Mitsuhiro
AU - Russell, Mary E.
AU - David, John R.
AU - Satoskar, Abhay R.
PY - 1998/12/1
Y1 - 1998/12/1
N2 - 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.
AB - 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.
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M3 - Article
VL - 161
SP - 6180
EP - 6188
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 11
ER -