Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.

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State: Public
Version: author
Serval ID
serval:BIB_843AC43D04A8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania.
Journal
PLoS neglected tropical diseases
Author(s)
Amelio P., Portevin D., Reither K., Mhimbira F., Mpina M., Tumbo A., Nickel B., Marti H., Knopp S., Ding S., Penn-Nicholson A., Darboe F., Ohmiti K., Scriba T.J., Pantaleo G., Daubenberger C., Perreau M.
ISSN
1935-2735 (Electronic)
ISSN-L
1935-2727
Publication state
Published
Issued date
07/2017
Peer-reviewed
Oui
Volume
11
Number
7
Pages
e0005817
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection.

Keywords
Adult, Animals, CD4-Positive T-Lymphocytes/immunology, Coinfection/immunology, Female, Helminthiasis/immunology, Helminths/isolation & purification, Humans, Interferon-gamma/blood, Male, Mycobacterium tuberculosis, South Africa, Tanzania, Th1-Th2 Balance, Tuberculosis, Pulmonary/immunology, Tumor Necrosis Factor-alpha/blood
Pubmed
Web of science
Open Access
Yes
Create date
08/08/2017 11:08
Last modification date
20/08/2019 14:43
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