PM2.5 impairs macrophage functions to exacerbate pneumococcus-induced pulmonary pathogenesis

Abstract

Background: Pneumococcus is one of the most common human airway pathogens that causes life-threatening infections. Ambient fine particulate matter (PM) with aerodynamic diameter ≤ 2.5 μm (PM 2.5) is known to significantly contribute to respiratory diseases. PM 2.5-induced airway inflammation may decrease innate immune defenses against bacterial infection. However, there is currently limited information available regarding the effect of PM 2.5 exposure on molecular interactions between pneumococcus and macrophages. Results: PM 2.5 exposure hampered macrophage functions, including phagocytosis and proinflammatory cytokine production, in response to pneumococcal infection. In a PM 2.5-exposed pneumococcus-infected mouse model, PM 2.5 subverted the pulmonary immune response and caused leukocyte infiltration. Further, PM 2.5 exposure suppressed the levels of CXCL10 and its receptor, CXCR3, by inhibiting the PI3K/Akt and MAPK pathways. Conclusions: The effect of PM 2.5 exposure on macrophage activity enhances pneumococcal infectivity and aggravates pulmonary pathogenesis.

Fine Particulate Matter Exposure Alters Pulmonary Microbiota Composition and Aggravates Pneumococcus-Induced Lung Pathogenesis

“…Macrophages play a crucial role in the clearance of pathogens. We recently demonstrated that PM 2.5 adversely influences macrophage activity to enhance pneumococcal infectivity and exacerbate pulmonary pathogenesis (Chen et al, 2020). Our results showed that PM 2.5 impairs macrophage functions, such as phagocytosis and cytokine production, resulting in reduction in its bacterial clearance activity.…”

“…Indeed, the histological analysis indicated severe pulmonary inflammation in mice with the combined treatment (PM + Sp). In addition, our recent study reported that macrophage functions were impaired by PM 2.5 exposure, which enhanced pneumococcal infectivity (Chen et al, 2020). These lines of evidence indicate that PM 2.5 alters the microbial ecosystem to benefit pneumococcus infection.…”

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“…The proteins of interest were detected by ECL Western blotting detection reagents (GE Healthcare, Piscataway, NJ, USA). The protein expression levels were analyzed using an Azure c400 system and AzureSpot Analysis Software (Azure Biosystems, Dublin, CA, USA) following the manufacturer's instructions [55].…”

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“…AGS cells (2 × 10 4 ) were cultured in 96-well plates for 16 h and incubated with rCdtC (200, 500, and 1,000 nM) at 37°C for 1, 7, and 11 h. The cells were then treated with 100 μl of 5 mg/ml 3-(4,5-dimethylthiazol-2-yl)–2,5-diphenyltetrazolium bromide (MTT) solution (Sigma-Aldrich, St. Louis, MO, United States) at 37°C for 2 h. The ability of viable cells to reduce MTT to formazan was measured ( Chen Y. W. et al, 2020 ). Cell viability was expressed as fold changes compared to the untreated group.…”