title: PD-L2 induction on dendritic cells exposed to Mycobacterium avium downregulates BCG-specific T cell response.
abstract: The exposure to certain species of Nontuberculous Mycobacteria (NTM) can modulate the immune response induced by Mycobacterium bovis BCG. Mycobacterium avium has been postulated as a weak inducer of dendritic cell (DC) maturation. However, how the DC exposure to M. avium could contribute to the modulation of a BCG-specific CD4+ T cell response and the molecules involved remain unknown. Here, we exposed bone marrow-derived DCs (BMDCs) to M. avium either prior to exposure to BCG or as a unique stimulus. We found that M. avium induces high expression of PD-L2 (B7-DC) in BMDCs. This was dependent on IL-10 production through the TLR2-p38 MAPK signaling pathway. Exposure to M. avium prior to BCG results in BMDCs that do not express co-stimulatory molecules and pro-inflammatory cytokines, while the expression of PD-L2 and IL-10 was maintained. BMDCs exposed to M. avium impaired the activation of BCG-specific T cells through the PD-1: PD-L interaction. This suggests that a M. avium-induced phenotype in DCs might be implicated in the induction of mechanisms of tolerance that could impact the T cell response induced by BCG vaccination.
authors.affiliation: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Edificio de Investigación 4 piso, Facultad de Medicina- Universidad Nacional Autonoma de México, Av. Universidad #3000, Coyoacán, 04630 México, DF Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mendoza-Coronel
authors.forename: Rosa
authors.initials: R
authors.lastname: Camacho-Sandoval
authors.forename: Laura C
authors.initials: LC
authors.lastname: Bonifaz
authors.forename: Yolanda
authors.initials: Y
authors.lastname: López-Vidal
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D016753:Interleukin-10 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium / Q000276:immunology*; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*
chemical_list: D001500:BCG Vaccine; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D016753:Interleukin-10