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The Mycobacterium tuberculosis glycoprotein Rv1016c protein inhibits dendritic cell maturation, and impairs Th1 /Th17 responses during mycobacteria infection.

Abstract：

:The myobacterial factors and the associated mechanism by which Mycobacterium tuberculosis (Mtb) evades the host immune surveillance system remain widely unexplored. Here, we found that overexpressing Rv1016c, a mannosylated protein of M. tuberculosis in BCG (rBCG-Rv1016c) led to increased virulence of the recombined BCG in the severe-combined immunodeficient (SCID) mice model and to a loss of protective efficacy in a zebrafish-M. marinum model, compared to wild type BCG. Further investigations on the effects of rBCG-Rv1016c on the host innate immunity revealed that rBCG-Rv1016c decreased the production of cytokines IL-2, IL-12p70, TGF-β, IL-6 as well as of the co-stimulatory molecules CD80, CD86, MHC-I and MHC-II by the infected DCs. These effects were mimicked by rBCG-Rv1016cHis, which carried an extra 6-His tag at the C-terminus of Rv1016c. Relatively to BCG infected DCs, the rBCG-Rv1016c-infected DCs failed to polarize naïve T cells to Th1- and Th17-type cells to secret IFN-γ and IL-17. Additionally, T lymphocytes from BCG- infected mice showed significantly less proliferation and production of IFN-γ and IL-17. Similarly, rBCG-Rv1016c mice released a higher level of IL-10 in response to rBCG-Rv1016c stimulation than wild type BCG infected mice. Furthermore, DCs from TLR-2 knockout mice showed no reduction in IL-6, IL-12 p70 and TGF-β secretion in response to rBCG-Rv1016c infection, compared to DCs infected with BCG. We propose that Rv1016c interferes in differentiation of the DCs by targeting suppressor of cytokine signaling (SOCS) 1 and SOCS3 expression, which subsequently leads to the reduction in STAT-1 and STAT-6 phosphorylation. These findings open new perspectives regarding the immunosuppressive strategies adopted by Mtb to survive in the host.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

Su H,Peng B,Zhang Z,Liu Z,Zhang Z

doi

10.1016/j.molimm.2019.02.021

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

58-70

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(18)30595-9

journal_volume

109

pub_type

杂志文章

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The Mycobacterium tuberculosis glycoprotein Rv1016c protein inhibits dendritic cell maturation, and impairs Th1 /Th17 responses during mycobacteria infection.