Effect of inhaled air pollution particulate matter in alveolar macrophages on local pro-inflammatory cytokine and peripheral interferon γ production in response to Mycobacterium tuberculosis
Authors: Yolanda Gonzalez, Claudia Carranza, Marco Iñiguez, Martha Torres, Raul Quintana, Alvaro Osornio, Carol Gardner, Srijata Sarkar, Stephan Schwander
Journal: The Lancet Global Health (2018)

BackgroundHuman alveolar macrophages are first-line cellular responders to inhaled particulate matter (PM) and microbial pathogens in the lungs. We examined whether PM exposure affects human bronchoalveolar and peripheral blood mononuclear cell responses to Mycobacterium tuberculosis.MethodsBronchoalveolar and peripheral blood mononuclear cells were obtained from 30 healthy adult volunteers living in Mexico City, Mexico. Proportions of alveolar macrophages with PM and areas of cytoplasm occupied by inhaled PM within alveolar macrophages were evaluated in 50 bronchoalveolar cells from each donor by ImageJ (version 1.49) on 1000× digital bright field microscopy cytospin images. Ambient PM2.5 (aerodynamic diameters <2·5 μm) was collected with high-volume samplers at the Instituto Nacional de Ecología y Cambio Climático, Mexico City. Frequencies of interleukin 1β, tumour necrosis factor (TNF) α, interleukin 6, and interferon-γ-producing bronchoalveolar and peripheral blood mononuclear cells stimulated with M tuberculosis (strain H37Ra at multiplicities of infection [MOI] of 1 and 10), lipopolysaccharide, 6 kDa early secretory antigenic target (ESAT-6), purified protein derivative, and PM2.5 were enumerated by ELISPOT assays.FindingsWhile 26–60% of bronchoalveolar cells harboured inhaled PM, percentages of alveolar macrophage areas covered by PM were between 0·9% (±0·16) and 5·49% (±0·78). In unstimulated bronchoalveolar cells and bronchoalveolar cells exposed in vitro to PM (PM2.5; 0·1, 1·0, 10 μg/mL), frequencies of interleukin-1β and TNF-α-producing cells decreased with higher percentages of alveolar macrophages containing inhaled PM (r=–0·78, p=0·0078 and r=–0·63, p=0·038, respectively). By contrast, frequencies of interferon-γ-producing cells increased in bronchoalveolar cells with alveolar macrophages containing greater areas of inhaled PM (r=0·59, p=0·049). In bronchoalveolar cells infected in vitro with M tuberculosis, frequencies of cells producing interleukin 1β significantly decreased in volunteers with higher percentages of alveolar macrophages containing inhaled PM. Frequencies of interferon-γ-producing cells were significantly decreased in peripheral blood mononuclear cells stimulated with purified protein derivative from volunteers with higher percentages of inhaled PM-containing alveolar macrophages (r=–0·7167, p=0·0184).InterpretationThe presence of inhaled PM in alveolar macrophages significantly decreases interleukin 1β and TNF-α production in bronchoalveolar cells in response to M tuberculosis infection as well as interferon-γ-production in peripheral blood mononuclear cells in response to purified protein derivative. These findings provide important insights into the potential mechanisms underlying the epidemiological observations of increased risk of tuberculosis development in air pollution exposure settings and indicate that air pollution may have an adverse impact on global tuberculosis control efforts.FundingNIEHS 5RO1ES020382-05.