Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

Abstract

ABSTRACTGlobal microplastic (MP) pollution is now well recognized, with humans and animals consuming and inhaling MPs on a daily basis. Herein we described the effects of azide-free, 1 µm polystyrene MP beads co-delivered into lungs with a SARS-CoV-2 omicron BA.5 inoculum using a mouse model of mild COVID-19. Lung virus titres and viral RNA levels were not significantly affected by MPs, with overt clinical or histopathological changes also not observed. However, RNA-Seq of infected lungs revealed that MP exposure suppressed innate immune responses at 2 days post infection (dpi) and increased pro-inflammatory signatures at 6 dpi. The cytokine profile at 6 dpi showed a significant correlation with the ‘cytokine release syndrome’ signature seen in some severe COVID-19 patients. This study adds to a growing body of literature suggesting that MPs can dysregulate inflammation in specific disease settings.Graphical AbstractHIGHLIGHTSA single inoculation of microplastics dysregulated SARS-CoV-2 lung inflammationAt the peak of SARS-CoV-2 infection microplastics decreased early innate responsesLater post infection microplastics promoted a “cytokine release syndrome” signatureA key mechanism may involve the inhibition of the phagocytosis of infected cellsAzide-free microplastics were used, with no elevated ROS responses identifiedPostulated mechanisms whereby microplastics might decrease the proinflammatory responses 2 days after SARS-CoV-2 infection, yet promote the proinflammatory ‘cytokine release syndrome’ signature at 6 days post infection.