Effects of engineered nanomaterial exposure on macrophage innate immune function

Abstract

Increasing use of engineered nanomaterials (ENMs) means increased human exposures. Potential adverse effects include those on the immune system, ranging from direct toxicity to impairment of defenses against environmental pathogens and toxins. Effects on lung macrophages may be especially prominent, because they serve to clear foreign materials like ENMs and bacterial pathogens. We investigated the effects of 4hour exposures over a range of concentrations, of a panel of industry-relevant ENMs, including SiO2, Fe2O3, ZnO, CeO2, TiO2, and an Ag/SiO2 composite, on human THP-1 macrophages. Effects on phagocytosis of latex beads, and phagocytosis and killing of Francisella tularensis (FT), as well as viability, oxidative stress and mitochondrial integrity, were measured by automated scanning confocal microscopy and image analysis. Results revealed some notable patterns: 1) Phagocytosis of unopsonized beads was increased, whereas that of opsonized beads was decreased, by all ENMs, with the exception of ZnO, which reduced both opsonized and unopsonized uptake; 2) Uptake of opsonized and unopsonized FT was either impaired or unaffected by all ENMs, with the exception of CeO2, which increased phagocytosis of unopsonized FT; 3) Macrophage killing of FT tended to improve with all ENMs; and 4) Viability was unaffected immediately following exposures with all ENMs tested, but was significantly decreased 24h after exposures to Ag/SiO2 and ZnO ENMs. The results reveal a complex landscape of ENM effects on macrophage host defenses, including both enhanced and reduced capacities, and underscore the importance of robust hazard assessment, including immunotoxicity assessment, of ENMs.