Abstract
Cell death and inflammation are intimately linked during mastitis due to Staphylococcus aureus (S. aureus). Pyroptosis, a programmed necrosis triggered by gasdermin protein family, often occurs after inflammatory caspase activation. Many pathogens invade host cells and activate cell-intrinsic death mechanisms, including pyroptosis, apoptosis, and necroptosis. We reported that bovine mammary epithelial cells (MAC-T) respond to S. aureus by NOD-like receptor protein 3 (NLRP3) inflammasome activation through K+ efflux, leading to the recruitment of apoptosis-associated speck-like protein (ASC) and the activation of caspase-1. The activated caspase-1 cleaves gasdermin D (GSDMD) and forms a N-terminal pore forming domain that drives swelling and membrane rupture. Membrane rupture results in the release of the pro-inflammatory cytokines IL-18 and IL-1β, which are activated by caspase-1. Can modulate GSDMD activation by NLRP3-dependent caspase-1 activation and then cause pyroptosis of bovine mammary epithelial cells.
Highlights
Staphylococcus aureus infection of the udder in dairy herds is a major cause of bovine mastitis
Bovine mastitis triggered by S. aureus infection remains a major problem in the dairy industry worldwide due to its pathogenicity, infectivity, colonization of skin or mucosal epithelium, persistence in the dairy environment, and poor therapeutic efficacy [19, 20]
Staphylococcus aureus can be ingested by bovine mammary epithelial cells, and intracellular S. aureus can escape endosomes and induce inflammation and cell death [21, 22]
Summary
Staphylococcus aureus infection of the udder in dairy herds is a major cause of bovine mastitis. Staphylococcus aureus is widespread in the natural environment of dairy farms; its adhesion and invasion of epithelial cells has made the treatment of mastitis difficult [3]. Pyroptosis is an inflammatory form of cell death caused by inflammasomes that can be triggered by a variety of stimuli, including bacterial infection and danger signals [5]. GSDMD of the gasdermin protein family is cleaved by inflammatory caspases and exhibits pore forming activity to drive pyroptosis [6, 7]. NLRP3 inflammasomes is an intracellular supramolecular complex composed of the sensor molecules NLRP3, ASC, and caspase-1 [10]. Caspase-1 can cleave pro-inflammatory cytokines IL-1β and IL-18 into mature
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