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Recombinant Lipoprotein Rv1016c derived from Mycobacterium tuberculosis is a TLR-2 ligand that induces macrophages apoptosis and inhibits MHC II antigen processing
- Source :
- Frontiers in Cellular and Infection Microbiology, Vol 6 (2016)
- Publication Year :
- 2016
- Publisher :
- Frontiers Media S.A., 2016.
-
Abstract
- TLR2-dependent cellular signaling in Mycobacterium tuberculosis-infected macrophages causes apoptosis and inhibits class II major histocompatibility complex (MHC-II) molecules antigen processing, leading to evasion of surveillance. Mycobacterium tuberculosis (Mtb) lipoproteins are an important class of Toll-like receptor (TLR) ligand, and identified as specific components that mediate these effects. In this study, we identified and characterized Mtb lipoprotein Rv1016c (lpqT) as a cell wall associated-protein that was exposed on the cell surface and enhanced the survival of recombinants M. smegmatis_Rv1016c under stress conditions. We found that Rv1016c lipoprotein was a novel TLR2 ligand and able to induce macrophage apoptosis in a both dose- and time-dependent manner. Additionally, apoptosis induced by Rv1016c was reserved in THP-1 cells blocked with anti-TLR-2 Abs or in TLR2-/- mouse macrophages, indicating that Rv1016c-induced apoptosis is dependent on TLR2. Moreover, we demonstrated that Rv1016c lipoprotein inhibited IFN-γ-induced MHC-II expression and processing of soluble antigens in a TLR2 dependent manner. Class II transactivator (CIITA) regulates MHC II expression. In this context, Rv1016c lipoprotein diminished IFN-γ-induced expression of CIITA IV through TLR2 and MAPK Signaling. TLR2-dependent apoptosis and inhibition of MHC-II Ag processing induced by Rv1016c during mycobacteria infection may promote the release of residual bacilli from apoptotic cells and decrease recognition by CD4+ T cells. These mechanisms may allow intracellular Mtb to evade immune surveillance and maintain chronic infection.
- Subjects :
- Apoptosis
Mycobacterium tuberculosis
TLR2
MHC II
Rv1061c
Microbiology
QR1-502
Subjects
Details
- Language :
- English
- ISSN :
- 22352988
- Volume :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Cellular and Infection Microbiology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.937a63533ec14385ba983a88ac8593b5
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fcimb.2016.00147