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Abstract
Numerous studies have examined the relationship between alveolar macrophages (AMs) and crystalline silica (SiO2) using in vitro and in vivo immunotoxicity models; however, exactly how exposure to SiO2 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 SiO2 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 SiO2 exposure (e.g., 4 h). Interestingly, these responses were dependent on interactions between SiO2 and the class A scavenger receptor CD204, but not MARCO. Furthermore, SiO2 exposure decreased uptake of fluorescently labeled Pam2CSK4 and Pam3CSK4, resulting in reduced secretion of IL-1β, but not IL-6. Collectively, our data suggest that SiO2 exposure alters AM phenotype, which in turn affects their ability to uptake and respond to bacterial lipoproteins.
Highlights
Silicon dioxide, known as silica, is one of the most common elements on earth, yet its inhalation can result in acute lung injury and ongoing inhalation can result in permanent lung damage due to deposition of particles in the lung
To test whether exposure of alveolar macrophages (AMs) in situ resulted in altered expression of pattern recognition receptors (PRRs), C57Bl/6 wild-type mice were instilled with either saline or 1 mg SiO2
Using bone marrow-derived macrophages as a model system [41], we demonstrate that SiO2-induced loss of TLR2 expression on F4-80+CD11b+ macrophages was dependent on CD204, but not MARCO at 4 h (Figure 3A) and 24 h post-exposure
Summary
Known as silica, is one of the most common elements on earth, yet its inhalation can result in acute lung injury and ongoing inhalation can result in permanent lung damage due to deposition of particles in the lung. Silicosis is a progressive, disabling, and often-fatal lung disease resulting from the inhalation of crystalline silica (SiO2) particles over prolonged periods of time. Silicosis occurs as the result of exposure through occupation (e.g., construction, mining), recreation (e.g., pottery), or environment (e.g., soil). Inhalation of SiO2 particles causes a granulomatous inflammatory response that progresses to interstitial fibrosis as well as systemic immune deficits [1,2,3,4,5]. There is no cure for silicosis, and treatment options are limited. Significant efforts have been made through industrial hygiene standards to control ambient dust in the workplace, silicosis remains a prevalent health problem throughout the world, in developing nations [6]
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