PINK1/parkin-mediated mitophagy alleviates Staphylococcus aureus-induced NLRP3 inflammasome and NF-KB pathway activation in bovine mammary epithelial cells

Staphylococcus aureus (S. aureus) is known to induce chronic and persistent bovine mammary infection, which affects milk quality and leads to premature culling. The ability of S. aureus to invade mammalian cells protects it from clearance by the immune system. Mitophagy is important in cell homeostasis, and can be utilized by pathogens for immune escape. However, mitophagy's role in S. aureus-associated bovine mastitis remains unclear. Here, S. aureus infection induced mitophagy and enhanced mitochondrial translocation of parkin in MAC-T cells. After mitophagy inhibition by Mdivi-1 treatment or PTEN-induced putative kinase 1 (PINK1) silencing in MAC-T cells infected with S. aureus, NOD-like receptor protein 3 (NLRP3) inflammasome activation and p65 and IKB alpha phosphorylation were increased. Meanwhile, PINK1 overexpression had the opposite effects. In addition, NLRP3 inflammasome overactivation and enhanced p65 and IKB alpha phosphorylation caused by PINK1 silencing were reversed by MitoTEMPO. Furthermore, PINK1/parkin-mediated mitophagy promoted S. aureus survival and contributed to persistent S. aureus infection. These findings provide new insights into S. aureus invasion in bovine mastitis.

Automated summary

Staphylococcus aureus (S. aureus) has the ability to invade mammalian cells and protect itself from clearance by the immune system. The role of mitophagy in S. aureus-associated bovine mastitis has been unclear. This study found that S. aureus infection induces mitophagy and enhances inflammation, contributing to S. aureus survival.