Air Pollution Particulate Matter Exposure Modulates Human Peripheral Blood Mononuclear Cell Host Immunity to Mycobacterium tuberculosis (M.tb)

Abstract

Abstract Epidemiological studies indicate that indoor air pollution exposure increases susceptibility to M.tb infection and Tuberculosis (TB) development. Recently, we demonstrated that diesel exhaust particles and urban air pollution particulate matter (PM) impair human peripheral blood mononuclear cell (PBMC) and respiratory epithelial cell (A549) innate immune responses to M.tb via downregulation of TLR-dependent cytokines (IFN-γ, IL-1β IL-6, TNF-α), and antimicrobial peptides, respectively. Here we examined effects of real-world-derived air pollution PM from Iztapalapa, a municipality with high prevalence of air pollution and TB in Mexico City on innate and adaptive human immune responses to M.tb. Cytotoxic and inflammatory PBMC responses were examined upon exposure to PM2.5 (<2.5μm diameter) and PM10 (<10μm) from rainy, cold-dry and warm-dry weather seasons. PBMC from IGRA+ (immunodiagnostic evidence of M.tb exposure) and IGRA- donors were exposed for 20 hours to PM at 0.1, 1 and 10 mg/mL followed by additional 20-hour M.tb exposure. A PM dose-dependent inhibition of IFN-γ production was observed in M.tb-infected PBMC from IGRA+ but not IGRA- donors. Furthermore, the size range of PM, but not their seasonal source, affected the M.tb-induced IFN-γ production. No PM dose-dependent inhibition of IL-1β production was observed in M.tb-infected PBMC from either IGRA+ or IGRA− donors. PM10 from cold-dry and warm-dry seasons at high concentration caused cytotoxicity. This data suggests that urban ambient air pollution PM exposure (1) modulates M.tb-induced adaptive immune responses (suppression of IFN-γ but not IL-1β production in IGRA+ donors) and (2) potentially alters M.tb infection outcomes. Funding NIEHS 5R01ES020382-05