PUBLICATION
The Mycobacterium tuberculosis glycoprotein Rv1016c protein inhibits dendritic cell maturation, and impairs Th1 /Th17 responses during mycobacteria infection
- Authors
- Su, H., Peng, B., Zhang, Z., Liu, Z., Zhang, Z.
- ID
- ZDB-PUB-190312-12
- Date
- 2019
- Source
- Molecular immunology 109: 58-70 (Journal)
- Registered Authors
- Keywords
- Dendritic cell, Glycosylated protein, Mycobacterium tuberculosis, Th1 cell response, Th17 cell response, Tuberculosis
- MeSH Terms
-
- Animals
- Bacterial Proteins/metabolism*
- Cell Differentiation*
- Cell Polarity
- Cytokines/metabolism
- Dendritic Cells/immunology*
- Dendritic Cells/microbiology
- Female
- Glycoproteins/metabolism*
- Mice
- Mycobacterium bovis/pathogenicity
- Mycobacterium tuberculosis/physiology*
- STAT Transcription Factors/metabolism
- Signal Transduction
- Spleen/pathology
- Suppressor of Cytokine Signaling 3 Protein/metabolism
- Th1 Cells/immunology*
- Th17 Cells/immunology*
- Toll-Like Receptor 2/metabolism
- Tuberculosis/immunology*
- Tuberculosis/microbiology
- Up-Regulation
- PubMed
- 30856410 Full text @ Mol. Immunol.
Citation
Su, H., Peng, B., Zhang, Z., Liu, Z., Zhang, Z. (2019) The Mycobacterium tuberculosis glycoprotein Rv1016c protein inhibits dendritic cell maturation, and impairs Th1 /Th17 responses during mycobacteria infection. Molecular immunology. 109:58-70.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping