Urban air PM modifies differently immune defense responses against bacterial and viral infections in vitro

Abstract

Epidemiological evidence has shown the association between exposure to ambient fine particulate matter (PM) and increased susceptibility to bacterial and viral respiratory infections. However, to date, the underlying mechanisms of immunomodulatory effects of PM remain unclear. Our objective was to explore how exposure to relatively low doses of urban air PM alters innate responses to bacterial and viral stimuli in vitro. We used secondary alveolar epithelial cell line along with monocyte-derived macrophages to replicate innate lung barrier in vitro . Co-cultured cells were first exposed for 24 hours to PM 2.5-1 (particle aerodynamic diameter between 1 and 2.5μm) and subsequently for an additional 24 hours to lipopolysaccharide (TLR4), polyinosinic-polycytidylic acid (TLR3), and synthetic single-stranded RNA oligoribonucleotides (TLR7/8) to mimic bacterial or viral stimulation. Toxicological endpoints included pro-inflammatory cytokines (IL-8, IL-6, and TNF-α), cellular metabolic activity, and cell cycle phase distribution. We show that cells exposed to PM 2.5-1 produced higher levels of pro-inflammatory cytokines following stimulation with bacterial TLR4 ligand than cells exposed to PM 2.5-1 or bacterial ligand alone. On the contrary, PM 2.5-1 exposure reduced pro-inflammatory responses to viral ligands TLR3 and TLR7/8. Cell cycle analysis indicated that viral ligands induced cell cycle arrest at the G2-M phase. In PM-primed co-cultures, however, they failed to induce the G2-M phase arrest. Contrarily, bacterial stimulation caused a slight increase in cells in the sub-G1 phase but in PM 2.5-1 primed co-cultures the effect of bacterial stimulation was masked by PM 2.5-1. These findings indicate that PM 2.5-1 may alter responses of immune defense differently against bacterial and viral infections. Further studies are required to explain the mechanism of immune modulation caused by PM in altering the susceptibility to respiratory infections.

Impacts of exposure to air pollution, radon and climate drivers on the COVID-19 pandemic in Bucharest, Romania: A time series study

“…Several scientific papers pointed out that short-term or long-term inhaled particulate matter containing radon progeny in both outdoor and indoor spaces may be associated with lung inflammation or neuroinflammation ( Asadi et al, 2020 ; Seposo et al, 2020 ; Blomberg et al, 2019 ; Keith et al, 2012 ; Seltenrich, 2019 ; Hosoda et al, 2021 ; Loffredo et al, 2021 ; Sugiyama et al, 2020 ), which in addition to SARS-COV-2 pathogens attached to aerosols, can lead to severe medical consequences, and contribute to increased COVID-19 mortality ( Macias-Verde et al, 2021 ; Maya et al, 2020 ). Changes in the air pollution and climate variables due to urbanization affect urban environmental health, and frequently increase the risk/hazard of viral infections probability ( Shahbaz et al, 2021 ; Domingo et al, 2020 ; Rebuli et al, 2021 ; Chong et al, 2022 ).…”

Mapping the Morbidity Risk Associated with Coal Mining in Queensland, Australia

“…Fine particle matter (PM 2.5 ) can deposit in the smallest sections of the respiratory system causing alveolar damage and can access the blood circulation to be uptaken by the vascular endothelium which can lead to endothelial dysfunction, both of which are mechanisms associated with respiratory and cardiovascular disease [5]. High levels of PM 2.5 are also linked to an altered inflammatory response associated with higher blood levels of cytokines, such as interleukin-6, interleukin-8 and tumour necrosis factor alpha that induce cellular necrosis or apoptosis and affect the transcription of genes [11,12]. Queensland has the second highest average ambient levels of particulate matter associated with coal mining in Australia [61] which can be linked to the higher risk of circulatory and respiratory diseases identified in our analysis.…”

“…Other releases from coal mining include fine particlebounded polycyclic aromatic hydrocarbons (PAHs) that have been associated with adverse effects in respiratory organs [9,10]. The mix of particles released in coal mining activities can determine diseases in exposed populations because of their ability to reach the smallest sections of the respiratory system and their potential effect on the endothelium and the inflammatory response [11,12].…”

Role of Macrophages in Air Pollution Exposure Related Asthma

“…Exposure to air pollutants provokes TLR expression and the further activation of macrophage response through PAMPs with DAMPs, a process known as priming [ 72 ]. Previous animal experimental studies have proven that exposure to air pollutants can provoke proinflammatory cytokine release via priming [ 52 ], and this process predominantly involves the TLR4 [ 43 , 44 , 63 , 73 , 74 , 75 , 76 ] and TLR2 [ 76 , 77 ] signaling pathways. Exposure to inhaled ozone results in increased expression of TLR4 and CD14 as well as the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) in healthy human macrophages [ 78 ].…”