T-bet and STAT1 regulate IFN-γ 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 STA1+/+ 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.
ASJC Scopus subject areas
- Immunology and Allergy