Short-term exposure to fine particulate matter exposure impairs innate immune and inflammatory responses to a pathogen stimulus: A functional study in the zebrafish model

Abstract

Short-term exposure to fine particulate matter (PM2.5) is associated with the activation of adverse inflammatory responses, increasing the risk of developing acute respiratory diseases, such as those caused by pathogen infections. However, the functional mechanisms underlying this evidence remain unclear. In the present study, we generated a zebrafish model of short-term exposure to a specific PM2.5, collected in the northern metropolitan area of Milan, Italy. First, we assessed the immunomodulatory effects of short-term PM2.5 exposure and observed that it elicited pro-inflammatory effects by inducing the expression of cytokines and triggering hyper-activation of both neutrophil and macrophage cell populations. Moreover, we examined the impact of a secondary infectious pro-inflammatory stimulus induced through the injection of Pseudomonas aeruginosa lipopolysaccharide (Pa-LPS) molecules after exposure to short-term PM2.5. In this model, we demonstrated that the innate immune response was less responsive to a second pro-inflammatory infectious stimulus. Indeed, larvae exhibited dampened leukocyte activation and impaired production of reactive oxygen species. The obtained results indicate that short-term PM2.5 exposure alters the immune microenvironment and affects the inflammatory processes, thus potentially weakening the resistance to pathogen infections.