Micro- and nanoplastics (MNPs) have been detected in diverse human organs such as the brain, heart, and kidneys, raising growing concern about their potential toxicity and systemic health impacts. Macrophages, key cells of the innate immune system and the first line of defence against foreign materials, are known to internalise micro- and nanoplastics (MNPs). However, the signalling pathways triggered in response to MNP uptake and the resulting effects on inflammatory responses, remain to be systematically characterised. Here we apply proteomics and microscopy experiments to study protein changes of macrophages upon incubation with MNPs.
Proteome analyses revealed an interferon-like response in the proteome of macrophages exposed to microplastic. Consistent with this observation, we detected increased phosphorylation of the inflammatory kinase TBK1, activation of the interferon pathway and upregulation of the interferon-stimulated gene GBP2 in microplastics-treated compared to nanoplastics-treated and control cells. In contrast, cholesterol biosynthesis-related proteins are markedly enriched in nanoplastics-treated macrophages.
We are currently investigating the underlying mechanisms of our observations using microscopy to map lipid distributions upon nanoplastic exposure and organellar changes that may drive the release of DNA into the cytosol and subsequent interferon responses upon microplastic exposure. Phosphoproteome and secretome experiments will further reveal how micro- and nanoplastics shape macrophage function and immune responses in an increasingly plastic-exposed world.