Acute Exposure to Crystalline Silica Reduces Macrophage Activation in Response to Bacterial Lipoproteins

Numerous studies have examined the relationship between alveolar macrophages (AMs) and crystalline silica (SiO(2)) using in vitro and in vivo immunotoxicity models; however, exactly how exposure to SiO(2) alters the functionality of AM and the potential consequences for immunity to respiratory pathogens remains largely unknown. Because recognition and clearance of inhaled particulates and microbes are largely mediated by pattern recognition receptors (PRRs) on the surface of AM, we hypothesized that exposure to SiO(2) limits the ability of AM to respond to bacterial challenge by altering PRR expression. Alveolar and bone marrow-derived macrophages downregulate TLR2 expression following acute SiO(2) exposure (e.g., 4 h). Interestingly, these responses were dependent on interactions between SiO(2) and the class A scavenger receptor CD204, but not MARCO. Furthermore, SiO(2) exposure decreased uptake of fluorescently labeled Pam(2)CSK(4) and Pam(3)CSK4, resulting in reduced secretion of IL-1β, but not IL-6. Collectively, our data suggest that SiO(2) exposure alters AM phenotype, which in turn affects their ability to uptake and respond to bacterial lipoproteins.