Abstract
Exposure to air pollution particulate matter (PM) and tuberculosis (TB) are two of the leading global public health challenges affecting low and middle income countries. An estimated 4.26 million premature deaths are attributable to household air pollution and an additional 4.1 million to outdoor air pollution annually. Mycobacterium tuberculosis (M.tb) infects a large proportion of the world’s population with the risk for TB development increasing during immunosuppressing conditions. There is strong evidence that such immunosuppressive conditions develop during household air pollution exposure, which increases rates of TB development. Exposure to urban air pollution has been shown to alter the outcome of TB therapy. Here we examined whether in vitro exposure to urban air pollution PM alters human immune responses to M.tb. PM2.5 and PM10 (aerodynamic diameters <2.5μm, <10μm) were collected monthly from rainy, cold-dry and warm-dry seasons in Iztapalapa, a highly populated TB-endemic municipality of Mexico City with elevated outdoor air pollution levels. We evaluated the effects of seasonality and size of PM on cytotoxicity and antimycobacterial host immunity in human peripheral blood mononuclear cells (PBMC) from interferon gamma (IFN-γ) release assay (IGRA)+ and IGRA- healthy study subjects. PM10 from cold-dry and warm-dry seasons induced the highest cytotoxicity in PBMC. With the exception of PM2.5 from the cold-dry season, pre-exposure to all seasonal PM reduced M.tb phagocytosis by PBMC. Furthermore, M.tb-induced IFN-γ production was suppressed in PM2.5 and PM10-pre-exposed PBMC from IGRA+ subjects. This observation coincides with the reduced expression of M.tb-induced T-bet, a transcription factor regulating IFN-γ expression in T cells. Pre-exposure to PM10 compared to PM2.5 led to greater loss of M.tb growth control. Exposure to PM2.5 and PM10 collected in different seasons differentially impairs M.tb-induced human host immunity, suggesting biological mechanisms underlying altered M.tb infection and TB treatment outcomes during air pollution exposures.
Highlights
Two preventable conditions, M.tb infection and air pollution exposure, still cause enormous loss of human life worldwide
Our findings suggest that exposure to urban outdoor air pollution particulate matter (PM) of different size ranges and from different seasons modulate M.tb-induced immune responses, corroborating epidemiological findings of air pollution exposure effects on M.tb infection outcomes in the real-world
Higher Ca concentrations were observed in PM10 than in PM2.5 samples, while V, Zn, Pb contents were higher in PM2.5 than PM10 samples
Summary
M.tb infection and air pollution exposure, still cause enormous loss of human life worldwide. Urban outdoor air pollution in cities is one of the main environmental public health risk factors and estimated to have caused 4.2 million premature deaths globally in 2016 [2]. Exposure to tobacco smoke [4,5,6,7,8] and household air pollution [9,10,11,12,13,14] increase the risk of TB development. Recent studies indicate that urban outdoor air pollution exposure increases the mortality of TB patients during TB therapy [15] and the risk of development of active TB [16, 17]. A potential link between long-term exposure to suspended particulate matter (PM) and increased rates of pulmonary TB has been reported in North Carolina where levels of air pollution are relatively low [18]
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