Background: Occupational exposure to crystalline silica is associated with an increased risk of developing lung pathology characterized by inflammation and fibrosis, which are believed to be starting points for the development of systemic events, such as systemic autoimmunity.

Objective: We aimed to investigate the differential effects of a (co)-exposure of silica and diesel exhaust particles (DEP) in C57BL/6J and autoimmune-prone NOD/ShiLtJ mice.

Methods: C57BL/6J and NOD/ShiLtJ mice were exposed to 4 doses of silica and/or DEP, or vehicle over 2 weeks. µCT scans were performed 8 weeks and 12 weeks post-exposure. Animals were sacrificed 12 weeks post-exposure to determine in vivo lung function. Lungs were collected for histological analyses and BALF to determine inflammatory parameters. Particle deposition and co-localization of silica and DEP were investigated using Raman spectroscopy.

Results: Silica and silica + DEP exposed C57BL/6J and NOD/ShiLtJ mice exhibited a local inflammatory reaction in lungs characterized by the presence of neutrophils, inflammatory infiltrates and collagen. Aerated lung volume was lower than that of control animals. BALF inflammatory cytokine levels were higher in silica and silica + DEP exposed mice compared to controls. Although airway hyperreactivity was not observed in any of the experimental groups of C57BL/6J mice, silica and silica + DEP exposed NOD/ShiLtJ mice showed airway hyperreactivity. Raman spectroscopy showed that DEP and silica particles co-localize within lung tissue.

Conclusion: Co-exposure of DEP with silica does not result in more pronounced effects compared to silica alone exposure. Exposed NOD/ShiLtJ exhibited more pronounced effects compared to C57BL/6J mice.