Open AccessMycobacterial glycolipid Di-O-acyl trehalose promotes a tolerogenic profile in dendritic cells
Author(s) -
Alejandro Magallanes-Puebla,
Patricia Espinosa-Cueto,
Luz M. López-Marı́n,
Raúl Mancilla
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0207202
Subject(s) - dendritic cell , trehalose , biology , antigen presentation , foxp3 , il 2 receptor , downregulation and upregulation , microbiology and biotechnology , antigen , t cell , immunology , chemistry , immune system , biochemistry , gene
Due to prolonged coevolution with the human being, Mycobacterium tuberculosis has acquired a sophisticated capacity to evade host immunity and persist in a latent state in the infected individual. As part of this evolutive process, mycobacteria have developed a highly complex cell wall that acts as a protective barrier. Herein we studied the effects of Di- O -acyl trehalose, a cell-wall glycolipid of virulent mycobacteria on murine bone marrow-derived dendritic cells. We have demonstrated that Di- O -Acyl-trehalose promotes a tolerogenic phenotype in bone marrow-derived murine DCs activated with mycobacterial antigens and Toll-like receptor agonists. This phenotype included low expression of antigen presentation and costimulatory molecules and altered cytokine production with downregulation of IL-12 and upregulation of IL-10, an anti-inflammatory cytokine. Additional markers of tolerogenicity were the expression of Indoleamine 2,3-dioxygenase and CD25. Furthermore, Di- O -Acyl-Trehalose promoted the expansion of FoxP3 + regulatory T lymphocytes. A better understanding of mycobacterial cell-wall components involved in the evasion of immunity is a prerequisite to designing better strategies to fight tuberculosis.