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Cutting Edge: STAT1 and T-bet Play Distinct Roles in Determining Outcome of Visceral Leishmaniasis Caused by Leishmania donovani¹

Lucia E. Rosas^2,*, Heidi M. Snider^2,*, Joseph Barbi^2,*, Anjali A. Satoskar, Geanncarlo Lugo-Villarino^||, Tracy Keiser^*, Tracy Papenfuss, Joan E. Durbin, Danuta Radzioch^¶, Laurie H. Glimcher^||,# and Abhay R. Satoskar^3,*,

^* Department of Microbiology, Department of Pathology, and Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, OH 43210; Department of Pediatrics, Children’s Hospital, Columbus, OH 43205; ^¶ Department of Experimental Medicine and Human Genetics, Montreal General Hospital, Montreal, Canada; ^|| Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115; and ^# Department of Medicine, Harvard Medical School, Boston, MA 02115

T-bet and STAT1 regulate IFN- 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.

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				L. M. Johnson and P. Scott STAT1 Expression in Dendritic Cells, but Not T Cells, Is Required for Immunity to Leishmania major J. Immunol., June 1, 2007; 178(11): 7259 - 7266. [Abstract] [Full Text] [PDF]