The Glycosylated Rv1860 Protein of Inhibits Dendritic Cell Mediated TH1 and TH17 Polarization of T Cells and Abrogates Protective Immunity Conferred by BCG

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Tuberculosis (TB), although recognized as an infectious disease for centuries, is still the leading cause of human deaths, claiming a million lives annually. Successful control of TB, either through drugs or effective preventive vaccines has not been achieved despite decades of research. We have studied the role for mannosylated protein Rv1860 of MTB in interfering with the early response of dendritic cells, which belong to the host's innate immune arsenal, to this mycobacterium. We were able to show that incorporating the gene coding for Rv1860 of MTB into the safe vaccine strain BCG resulted in loss of BCG's protective ability in the guinea pig animal model. Using primary mouse bone marrow derived dendritic cells in vitro as well as spleen dendritic cells from infected mice, we show in this study that exposure to mannosylated Rv1860 leads to loss of dendritic cell functions such as cytokine secretion and T cell activation. This leads to defective downstream T cell responses to the mycobacteria. We suggest that altering or extinguishing the expression of such glycoproteins by mycobacteria may be a strategy for developing better vaccines against TB.

Vyšlo v časopise: The Glycosylated Rv1860 Protein of Inhibits Dendritic Cell Mediated TH1 and TH17 Polarization of T Cells and Abrogates Protective Immunity Conferred by BCG. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004176
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004176

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