Cutting edge: STAT1 and T-bet play distinct roles in determining outcome of visceral leishmaniasis caused by Leishmania donovani.
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.
Rosas
Lucia E
LE
Department of Microbiology, Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA.
Snider
Heidi M
HM
Barbi
Joseph
J
Satoskar
Anjali A
AA
Lugo-Villarino
Geanncarlo
G
Keiser
Tracy
T
Papenfuss
Tracy
T
Durbin
Joan E
JE
Radzioch
Danuta
D
Glimcher
Laurie H
LH
Satoskar
Abhay R
AR
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000469:parasitology; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000235:genetics / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000235:genetics / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020825:T-Box Domain Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000098815:T-bet Transcription Factor
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors