Rivas-Santiago César E, Sarkar Srijata, Cantarella Pasquale, Osornio-Vargas Álvaro, Quintana-Belmares Raúl, Meng Qingyu, Kirn Thomas J, Ohman Strickland Pamela, Chow Judith C, Watson John G, Torres Martha, Schwander Stephan
Rutgers School of Public Health, Department of Environmental and Occupational Health, Piscataway, New Jersey, USA.
Department of Pediatrics, University of Alberta, ECHA, Edmonton, AB, Canada.
Infect Immun. 2015 Jun;83(6):2507-17. doi: 10.1128/IAI.03018-14. Epub 2015 Apr 6.
Inhalation exposure to indoor air pollutants and cigarette smoke increases the risk of developing tuberculosis (TB). Whether exposure to ambient air pollution particulate matter (PM) alters protective human host immune responses against Mycobacterium tuberculosis has been little studied. Here, we examined the effect of PM from Iztapalapa, a municipality of Mexico City, with aerodynamic diameters below 2.5 μm (PM2.5) and 10 μm (PM10) on innate antimycobacterial immune responses in human alveolar type II epithelial cells of the A549 cell line. Exposure to PM2.5 or PM10 deregulated the ability of the A549 cells to express the antimicrobial peptides human β-defensin 2 (HBD-2) and HBD-3 upon infection with M. tuberculosis and increased intracellular M. tuberculosis growth (as measured by CFU count). The observed modulation of antibacterial responsiveness by PM exposure was associated with the induction of senescence in PM-exposed A549 cells and was unrelated to PM-mediated loss of cell viability. Thus, the induction of senescence and downregulation of HBD-2 and HBD-3 expression in respiratory PM-exposed epithelial cells leading to enhanced M. tuberculosis growth represent mechanisms by which exposure to air pollution PM may increase the risk of M. tuberculosis infection and the development of TB.
吸入室内空气污染物和香烟烟雾会增加患结核病(TB)的风险。暴露于环境空气污染颗粒物(PM)是否会改变人体对结核分枝杆菌的保护性宿主免疫反应,目前研究较少。在此,我们研究了来自墨西哥城伊萨帕拉帕市的空气动力学直径低于2.5μm(PM2.5)和10μm(PM10)的颗粒物对A549细胞系人肺泡II型上皮细胞固有抗分枝杆菌免疫反应的影响。暴露于PM2.5或PM10会破坏A549细胞在感染结核分枝杆菌后表达抗菌肽人β-防御素2(HBD-2)和HBD-3的能力,并增加细胞内结核分枝杆菌的生长(通过菌落形成单位计数测量)。观察到的PM暴露对抗菌反应性的调节与暴露于PM的A549细胞衰老的诱导有关,与PM介导的细胞活力丧失无关。因此,暴露于呼吸道PM的上皮细胞中衰老的诱导以及HBD-2和HBD-3表达的下调导致结核分枝杆菌生长增强,这代表了暴露于空气污染PM可能增加结核分枝杆菌感染风险和结核病发生的机制。