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Signal transducer and activator of transcription 1 (STAT‐1) plays a critical role in control of Trypanosoma cruzi infection
Author(s) -
Kulkarni Manjusha M.,
Varikuti Sanjay,
Terrazas Cesar,
Kimble Jennifer L.,
Satoskar Abhay R.,
McGwire Bradford S.
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12438
Subject(s) - stat protein , stat , biology , stat4 , trypanosoma cruzi , immunology , intracellular parasite , cytokine , knockout mouse , interferon , jak stat signaling pathway , interleukin 10 , intracellular , signal transduction , microbiology and biotechnology , immune system , stat3 , receptor , parasite hosting , biochemistry , tyrosine kinase , world wide web , computer science
Summary 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 CD 4, CD 8 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.