Fig. 16

Synergistic effects of diesel exhaust particles (DEP) and high-fat (HF) diet results in increased reactive oxygen and nitrogen species (ROS + RNS) produced possibly by macrophages, which increases nitrates within the lung environment. These nitrates provide nutrients for anaerobic respiration and selective growth of Proteobacteria within the lungs resulting in alterations in the commensal microbial composition. Both DEP and the bacterial alterations could activate Toll-like receptors (TLRs) which results in the subsequent activation of NF-κB mediated inflammatory gene transcription. Since NF-κB signaling is understood to be required for sustained cytokine expression in macrophages, the production of inflammatory cytokines, ROS, and RNS is sustained, resulting in a continuous cycle of inflammation and microbial shifts throughout the duration of DEP exposures. This sustained and persistent inflammation is a possible contributor and significant in the development of lung diseases