Cruz-Aguilar Marisa, Castillo-Rodal Antonia I, Schcolnik-Cabrera Alejandro, Bonifaz Laura C, Molina Gabriela, López-Vidal Yolanda
Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de Mexico, Mexico.
Unidad de Investigación Médica en Inmunoquímica, Instituto Mexicano del Seguro Social, México, DF, Mexico.
Tuberculosis (Edinb). 2016 Jul;99:31-40. doi: 10.1016/j.tube.2016.04.003. Epub 2016 Apr 13.
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.
非结核分枝杆菌（NTM）被认为是新兴病原体，其免疫调节机制尚未得到充分描述。其中，鸟分枝杆菌已知是树突状细胞（DCs）的弱激活剂，会损害卡介苗诱导的反应。然而，其他非结核分枝杆菌，如瘰疬分枝杆菌是否会调节DCs的激活，尚未得到广泛研究。在此，我们将骨髓来源的DCs（BMDCs）暴露于瘰疬分枝杆菌，并分析其对DCs激活的影响。我们发现，瘰疬分枝杆菌具有类似的诱导半成熟DC表型的能力，这是通过其与DC-SIGN和TLR4受体的协同作用产生的。暴露于瘰疬分枝杆菌的BMDCs显示出PD-L2的高表达和IL-10的产生，以及共刺激分子和促炎细胞因子的低水平。除了在DCs上诱导的免疫表型外，形态学变化、细胞骨架重组和迁移能力下降与半成熟表型一致。然而，与其他致病性分枝杆菌不同，再次暴露于卡介苗后，瘰疬分枝杆菌诱导的DC半成熟表型会逆转，这表明瘰疬分枝杆菌使用的DC激活调节机制与其他已知致病性分枝杆菌不同。这是关于瘰疬分枝杆菌刺激DCs的免疫表型特征的首次报告。
