Innate Immune Responses to Nanoparticle Exposure in the Lung

Abstract

The nanotechnology revolution offers enormous societal and economic benefits for innovation in the fields of engineering, electronics, and medicine. Nevertheless, evidence from rodent studies show that biopersistent engineered nanomaterials (ENMs) stimulate immune, inflammatory, and fibroproliferative responses in the lung, suggesting possible risks for lung diseases or systemic immune disorders as a consequence of occupational, environmental, or consumer exposure. Due to their nanoscale dimensions and increased surface area per unit mass, ENMs have a much greater potential to reach the distal regions of the lung and generate ROS. High aspect ratio ENMs (e.g., nanotubes, nanofibers) activate inflammasomes in macrophages, triggering IL-1β release and neutrophilic infiltration into the lungs. Moreover, some ENMs alter allergen-induced eosinophilic inflammation by immunostimulation, immunosuppression, or modulating the balance between Th1, Th2, and Th17 cells, thereby influencing the nature of the inflammatory response. ENMs also migrate from the lungs across epithelial, endothelial, or mesothelial barriers to stimulate or suppress systemic immune responses.

Keywords: asthma; innate immunity; lung; nanoparticles.

Figure 1

Illustration summarizing some of the effects of metal oxide nanoparticles (NPs) or carbon nanotubes (CNTs) on airway remodeling in asthma. In normal healthy lungs, Metal NPs (e.g., TiO₂, NiO, ZnO) or CNTs (single- or multi-walled CNTs) stimulate a Th1 inflammatory response characterized by IFN-γ production, classic macrophage activation, neutrophilic infiltration, and fibrosis. Under conditions of pre-existing allergen-induced airway inflammation (i.e., asthma), NPs or CNTs enhance allergen-induced mucus production, modulate allergen-induced airway fibrosis, and alter allergen-induced Th2 responses and eosinophilic inflammation to produce a mixed inflammatory cell immune response.

Figure 2

llustration showing postulated effects of carbon nanotubes (CNTs) or nickel nanoparticles (NiNPs) on pleural inflammation. CNTs or NiNPs taken up by macrophages traffic to the subpleura or exit the lung via lymphatic ducts and produce PDGF to signal mesothelial cell secretion of chemokines (CCL2, CXCL10) that mediate mononuclear cell accumulation at the pleural surface (see ref 9). The inset shows the interaction between a CNT- or NiNP-activated macrophages and a mesothelial cell. Macrophage-derived PDGF stimulates MAP kinase activation in mesothelial cells and NiNPs prolong PDGF-induced MAP kinase activation, leading to synergistic increases in chemokine production (see ref 64).