Rosas Lucia E, Snider Heidi M, Barbi Joseph, Satoskar Anjali A, Lugo-Villarino Geanncarlo, Keiser Tracy, Papenfuss Tracy, Durbin Joan E, Radzioch Danuta, Glimcher Laurie H, Satoskar Abhay R
Department of Microbiology, Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA.
J Immunol. 2006 Jul 1;177(1):22-5. doi: 10.4049/jimmunol.177.1.22.
T-bet and STAT1 regulate IFN-gamma gene transcription in CD4+ T cells, which mediate protection against Leishmania. Here we show that T-bet and STAT1 are required for the induction of an efficient Th1 response during Leishmania donovani infection, but they play distinct roles in determining disease outcome. Both STAT1(-/-) and T-bet(-/-) mice failed to mount a Th1 response, but STAT1(-/-) mice were highly resistant to L. donovani and developed less immunopathology, whereas T-bet(-/-) mice were highly susceptible and eventually developed liver inflammation. Adoptive cell transfer studies showed that RAG2(-/-) recipients receiving STAT1(+/+) or STAT1(-/-) T cells developed comparable liver pathology, but those receiving STAT1(-/-) T cells were significantly more susceptible to infection. These unexpected findings reveal distinct roles for T-bet and STAT1 in mediating host immunity and liver pathology during visceral leishmaniasis.
T-bet和STAT1调节CD4 + T细胞中的IFN-γ基因转录，这些细胞介导对利什曼原虫的保护作用。我们在此表明，T-bet和STAT1是杜氏利什曼原虫感染期间诱导有效Th1反应所必需的，但它们在决定疾病结局中发挥着不同的作用。STAT1(-/-)和T-bet(-/-)小鼠均未能产生Th1反应，但STAT1(-/-)小鼠对杜氏利什曼原虫具有高度抗性，且免疫病理学发展较轻，而T-bet(-/-)小鼠则高度易感并最终发展为肝脏炎症。过继性细胞转移研究表明，接受STAT1(+/+)或STAT1(-/-) T细胞的RAG2(-/-)受体出现了相当的肝脏病理变化，但接受STAT1(-/-) T细胞的受体对感染的易感性明显更高。这些意外发现揭示了T-bet和STAT1在内脏利什曼病中介导宿主免疫和肝脏病理过程中的不同作用。
