title: Signal transducer and activator of transcription 1 (STAT-1) plays a critical role in control of Trypanosoma cruzi infection.
abstract: The control of Trypanosoma cruzi infection is related to interferon-γ (IFN-γ) activation leading to intracellular clearance of parasites. The transcription factor signal transducer and activator of transcription 1 (STAT-1) is a key mediator of IFN-γ intracellular signalling and knockout of this protein leads to susceptibility to several intracellular microbes. To determine the role of STAT-1 in host susceptibility to T. cruzi infection we compared the survival, parasite loads and balance of IFN-γ and interleukin-10 (IL-10) responses between wild-type and STAT-1 knockout mice. We found that the lack of STAT-1 resulted in a more robust infection, leading to higher levels of blood and tissue parasites and markedly reduced survival. In addition, infected STAT-1 knockout mice had higher systemic levels of both IFN-γ and IL-10, suggesting that the absence of STAT-1 leads to a disequilibrium of pro-inflammatory and anti-inflammatory cytokines. Analysis of spleen cells indicates that CD4, CD8 cells generate IFN-γ and natural killer cells express IL-13 in STAT-1 knockout animals. The production of IL-17 is particularly enhanced in the absence STAT-1 expression but did not reduce mortality. Overall these results indicate that STAT-1 is important for the control of T. cruzi infection in mice.
authors.affiliation: Center for Microbial Interface Biology, The Ohio State University Medical Center, Columbus, OH, USA; Department of Microbial Infection and Immunity, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Manjusha M
authors.initials: MM
authors.lastname: Kulkarni
authors.forename: Sanjay
authors.initials: S
authors.lastname: Varikuti
authors.forename: Cesar
authors.initials: C
authors.lastname: Terrazas
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kimble
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
authors.forename: Bradford S
authors.initials: BS
authors.lastname: McGwire
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D014355:Chagas Disease / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D016207:Cytokines; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse
keywords: STAT-1; Trypanosoma cruzi; immune response; infection