Inhaled Particulate Matter Exposure Worsens the Outcome of Influenza Infection Through Direct Effects on Macrophages 2259112

Abstract Introduction Air pollution is a global health problem associated with increased morbidity and mortality from respiratory diseases, particularly in the elderly, due to the inhalation of particulate matter. However, the mechanisms of how particulate exposure affects lung immunity is not well understood. Methods We developed a mouse model of particulate matter (PM) exposure to evaluate its impact on respiratory immunity. Young (8-12 weeks) and aged (70-80 weeks) mice were divided into four groups: naïve, PM only, PR8 only, and PM+PR8. PM groups received intranasal PM for two weeks (5 days of treatment and 2 days of rest), followed by intranasal PR8 influenza infection delivered in PBS (PR8 only) or in PM solution (PM+PR8). PM exposure continued post-infection. Lungs were isolated 4 days post infection (dpi) and analyzed by confocal microscopy, flow cytometry and multiplex cytokine profiling. Results Both young and aged mice exposed to PM exhibited increased morbidity following influenza infection compared to infection alone, indicating that particulate exposure exacerbates viral responses. Histological and multiplex analyses of lungs at 4 days post infection revealed reduced alveolar space with interstitial and intra-alveolar inflammation in both age groups, with notably increased mucus production in young mice. PM exposure with PR8 infection also induced age-specific cytokine and chemokine upregulation, fostering a pro-inflammatory environment. PM was predominantly contained within alveolar macrophages, which exhibited an increased pro-inflammatory phenotype and reduced expression of regulatory markers following PM challenge with PR8 infection. Conclusion These findings demonstrate that PM exposure primes the lung for heightened inflammation and worsened outcomes following respiratory viral infection. Funding Source NIH Grant: 5K01AG078439-03 (Ural, BB) Topic Categories Mucosal and Regional Immunology (MUC)