Cutting edge: STAT1 and T-bet play distinct roles in determining outcome of visceral leishmaniasis caused by Leishmania donovani

J Immunol. 2006 Jul 1;177(1):22-5. doi: 10.4049/jimmunol.177.1.22.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Genetic Predisposition to Disease
  • Immunity, Innate / genetics
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / parasitology
  • Leishmania donovani / immunology*
  • Leishmaniasis, Visceral / genetics
  • Leishmaniasis, Visceral / immunology*
  • Leishmaniasis, Visceral / parasitology*
  • Leishmaniasis, Visceral / pathology
  • Liver Diseases, Parasitic / genetics
  • Liver Diseases, Parasitic / immunology
  • Liver Diseases, Parasitic / parasitology
  • Liver Diseases, Parasitic / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • STAT1 Transcription Factor / deficiency
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / physiology*
  • T-Box Domain Proteins
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / transplantation
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors