Interactions between particulate matter and bacteria during cowshed PM-induced respiratory injury initiates GBP2/Caspase-11/NLRP3-mediated intracellular bacterial defense and pyroptosis.

Abstract

INTRODUCTION: Fine particulate matter (PM) is an important factor in the induction of a variety of respiratory diseases and associated cellular damage. The composition of PMin the animal farm environments is complex, which poses a significant threat to the respiratory health of both workers and livestock, but the causative mechanisms are unclear. METHODS: In order to investigate targeted treatment options, this study focused on the role of microbial components in cowshed PM-induced respiratory damage. Utilizing the common pathogenic bacteria () in cowshed PMas a perspective, the intrinsic connection and interaction mechanism between PMparticles and bacterial components were explored throughandexperiments. Bacterial components can interact with PMand are important factors in the respiratory toxicity of PMin farm animal environments by scanning electron microscopy (SEM), Fourier infrared spectroscopy (FTIR) and Zeta potential measurements. RESULTS: We demonstrate that Bacteria adhered to PMparticles and modified the original surface functional groups characteristics, significantly enhanced toxic effects of PMon cells (including oxidative stress levels, release of inflammatory factors, etc.). Furthermore, PMparticles significantly enhanced bacterial intracellular invasion, initiated the guanylate-binding protein 2 (GBP2)-mediated intracellular bacterial defense mechanism, further triggered the non-canonical NLRP3 pathway, and ultimately induced a cascade of inflammatory responses and pyroptosis. To explore therapeutic strategies, siRNA silencing of GBP2 and inhibition of NLRP3 were done; GBP2 silencing initially delayed cytotoxicity, but eventually increased the inflammatory response. However, inhibition of NLRP3 expression maintained cell viability and delayed pyroptosis, with potential as an effective solution for treatment of PM-induced lung injury in farm-animal environments. CONCLUSION: In conclusion, the results of this study demonstrated the interaction between particulate matter and bacteria during cowshed PM-induced respiratory injury and clarified the signaling mechanisms among intracellular bacteria, GBP2, NLRP3, and pyroptosis. These findings provide a theoretical basis for developing therapeutic strategies against PM-related respiratory diseases in farm-animal environments.