Format

Send to

Choose Destination
See comment in PubMed Commons below
Mediators Inflamm. 2014;2014:914326. doi: 10.1155/2014/914326. Epub 2014 Jul 24.

Myocardial gene expression of T-bet, GATA-3, Ror-γt, FoxP3, and hallmark cytokines in chronic Chagas disease cardiomyopathy: an essentially unopposed TH1-type response.

Author information

  • 1Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, 01246-903 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (iii), INCT, University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
  • 2Division of Surgery, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
  • 3Division of Pathology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
  • 4Transplantation and Heart Failure Unit, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.

Abstract

BACKGROUND:

Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg) in CCC, NIC, and heart donor myocardial samples.

METHODS AND RESULTS:

Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-β and IL-10) were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4.

CONCLUSIONS:

Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3(+)CTLA4(+) Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Hindawi Publishing Corporation Icon for PubMed Central
    Loading ...
    Write to the Help Desk