title: TLR4 and DC-SIGN receptors recognized Mycobacterium scrofulaceum promoting semi-activated phenotype on bone marrow dendritic cells.
abstract: Nontuberculous mycobacteria (NTM) are recognized as emerging pathogens and their immune regulatory mechanisms are not well described yet. From them, Mycobacterium avium is known to be a weak activator of dendritic cells (DCs) that impairs the response induced by BCG vaccine. However, whether other NTM such as Mycobacterium scrofulaceum may modulate the activation of DCs, has not been extensively studied. Here, we exposed bone marrow-derived DCs (BMDCs) to M. scrofulaceum and we analyzed the effect on the activation of DCs. We found that M. scrofulaceum has a comparable ability to induce a semi-mature DC phenotype, which was produced by its interaction with DC-SIGN and TLR4 receptors in a synergic effect. BMDCs exposed to M. scrofulaceum showed high expression of PD-L2 and production of IL-10, as well as low levels of co-stimulatory molecules and pro-inflammatory cytokines. In addition to immunophenotype induced on DCs, changes in morphology, re-organization of cytoskeleton and decreased migratory capacity are consistent with a semi-mature phenotype. However, unlike other pathogenic mycobacteria, the DC-semi-mature phenotype induced by M. scrofulaceum was reversed after re-exposure to BCG, suggesting that modulation mechanisms of DC-activation used by M. scrofulaceum are different to other known pathogenic mycobacteria. This is the first report about the immunophenotypic characterization of DC stimulated by M. scrofulaceum.
authors.affiliation: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico. Electronic address: maricruzmca1804@yahoo.com.
authors.forename: Marisa
authors.initials: M
authors.lastname: Cruz-Aguilar
authors.affiliation: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico. Electronic address: castillorodal@gmail.com.
authors.forename: Antonia I
authors.initials: AI
authors.lastname: Castillo-Rodal
authors.affiliation: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico. Electronic address: a.schcolnik@garvan.org.au.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Schcolnik-Cabrera
authors.affiliation: Unidad de Investigación Médica en Inmunoquímica, Instituto Mexicano del Seguro Social, México, DF, Mexico. Electronic address: labonifaz@yahoo.com.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Bonifaz
authors.affiliation: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico. Electronic address: gabriela.molina86@yahoo.com.mx.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Molina
authors.affiliation: Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico. Electronic address: lvidal@unam.mx.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: López-Vidal
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015815:Cell Adhesion Molecules / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium / Q000276:immunology; D015359:Mycobacterium scrofulaceum / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D010641:Phenotype; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000276:immunology / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D001500:BCG Vaccine; D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; D016753:Interleukin-10; D037181:Lectins, C-Type; D061027:Programmed Cell Death 1 Ligand 2 Protein; D019908:Proto-Oncogene Proteins c-raf; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C556062:IL10 protein, mouse; C556978:Pdcd1lg2 protein, mouse; C493487:Tlr4 protein, mouse
keywords: DC maturation; Dendritic cells; Innate immunology; M. scrofulaceum