ArticlePLoS pathogens2014
The glycosylated Rv1860 protein of Mycobacterium tuberculosis inhibits dendritic cell mediated TH1 and TH17 polarization of T cells and abrogates protective immunity conferred by BCG.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Recent Characterization of Key Proteins to Combat Tuberculosis.Advances in experimental medicine and biology · 2026Review
- Immune Response to the Recombinant Apa Protein from Mycobacterium tuberculosis Expressed in Streptomyces lividans After Intranasal Administration in Mice. Induction of Protective Response to Tubercle Bacillus Aerosols Exposure.Current microbiology · 2024Article
- Extracellular Vesicles and Immune System in Ageing and Immune Diseases.Experimental neurobiology · 2021Review
- Ample glycosylation in membrane and cell envelope proteins may explain the phenotypic diversity and virulence in the Mycobacterium tuberculosis complex.Scientific reports · 2019Article
- cGAS/STING/TBK1/IRF3 Signaling Pathway Activates BMDCs Maturation FollowingInternational journal of molecular sciences · 2019Article
- FuFangChangTai Decoction Activates Macrophages via Inducing Autophagy.Evidence-based complementary and alternative medicine : eCAM · 2019Article
- Deletion of BCG Hip1 protease enhances dendritic cell and CD4 T cell responses.Journal of leukocyte biology · 2018Article
- Rhodococcus erythropolis as a host for expression, secretion and glycosylation of Mycobacterium tuberculosis proteins.Microbial cell factories · 2017Article
- Emerging facets of prokaryotic glycosylation.FEMS microbiology reviews · 2017Review
- Immune Responses to Bacillus Calmette-Guérin Vaccination: Why Do They Fail to Protect againstFrontiers in immunology · 2017Review
- Giving CD4+ T cells the slip: viral interference with MHC class II-restricted antigen processing and presentation.Current opinion in immunology · 2016Review
- Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.Scientific reports · 2016Article
- The Secreted Protein Rv1860 of Mycobacterium tuberculosis Stimulates Human Polyfunctional CD8+ T Cells.Clinical and vaccine immunology : CVI · 2016Article
- Recombinant Lipoprotein Rv1016c Derived fromFrontiers in cellular and infection microbiology · 2016Article
- IL-1β, But Not Programed Death-1 and Programed Death Ligand Pathway, Is Critical for the Human Th17 Response toFrontiers in immunology · 2016Article
- CHO expressed recombinant human lactoferrin as an adjuvant for BCG.International journal of immunopathology and pharmacology · 2015Article
- The presence of a galactosamine substituent on the arabinogalactan of Mycobacterium tuberculosis abrogates full maturation of human peripheral blood monocyte-derived dendritic cells and increases secretion of IL-10.Tuberculosis (Edinburgh, Scotland) · 2015Article
- The interaction of mycobacterial protein Rv2966c with host chromatin is mediated through non-CpG methylation and histone H3/H4 binding.Nucleic acids research · 2015Article
- Virulence-Dependent Alterations in the Kinetics of Immune Cells during Pulmonary Infection by Mycobacterium tuberculosis.PloS one · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously reported interferon gamma secretion by human CD4⁺ and CD8⁺ T cells in response to recombinant E. coli-expressed Rv1860 protein of Mycobacterium tuberculosis (MTB) as well as protection of guinea pigs against a challenge with virulent MTB following prime-boost immunization with DNA vaccine and poxvirus expressing Rv1860. In contrast, a Statens Serum Institute Mycobacterium bovis BCG (BCG-SSI) recombinant expressing MTB Rv1860 (BCG-TB1860) showed loss of protective ability compared to the parent BCG strain expressing the control GFP protein (BCG-GFP). Since Rv1860 is a secreted mannosylated protein of MTB and BCG, we investigated the effect of BCG-TB1860 on innate immunity. Relative to BCG-GFP, BCG-TB1860 effected a significant near total reduction both in secretion of cytokines IL-2, IL-12p40, IL-12p70, TNF-α, IL-6 and IL-10, and up regulation of co-stimulatory molecules MHC-II, CD40, CD54, CD80 and CD86 by infected bone marrow derived dendritic cells (BMDC), while leaving secreted levels of TGF-β unchanged. These effects were mimicked by BCG-TB1860His which carried a 6-Histidine tag at the C-terminus of Rv1860, killed sonicated preparations of BCG-TB1860 and purified H37Rv-derived Rv1860 glycoprotein added to BCG-GFP, but not by E. coli-expressed recombinant Rv1860. Most importantly, BMDC exposed to BCG-TB1860 failed to polarize allogeneic as well as syngeneic T cells to secrete IFN-γ and IL-17 relative to BCG-GFP. Splenocytes from mice infected with BCG-SSI showed significantly less proliferation and secretion of IL-2, IFN-γ and IL-17, but secreted higher levels of IL-10 in response to in vitro restimulation with BCG-TB1860 compared to BCG-GFP. Spleens from mice infected with BCG-TB1860 also harboured significantly fewer DC expressing MHC-II, IL-12, IL-2 and TNF-α compared to mice infected with BCG-GFP. Glycoproteins of MTB, through their deleterious effects on DC may thus contribute to suppress the generation of a TH1- and TH17-dominated adaptive immune response that is vital for protection against tuberculosis.
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