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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.
AuthorsManjusha M Kulkarni, Sanjay Varikuti, Cesar Terrazas, Jennifer L Kimble, Abhay R Satoskar, Bradford S McGwire
JournalImmunology (Immunology) Vol. 145 Issue 2 Pg. 225-31 (Jun 2015) ISSN: 1365-2567 [Electronic] England
PMID25545325 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2014 John Wiley & Sons Ltd.
Chemical References
  • Cytokines
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
Topics
  • Animals
  • CD4-Positive T-Lymphocytes (immunology)
  • CD8-Positive T-Lymphocytes (immunology)
  • Chagas Disease (genetics, immunology)
  • Cytokines (genetics, immunology)
  • Female
  • Mice
  • Mice, Knockout
  • STAT1 Transcription Factor (genetics, immunology)
  • Trypanosoma cruzi (immunology)

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