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

Int Immunopharmacol. 2022 Nov:112:109200. doi: 10.1016/j.intimp.2022.109200. Epub 2022 Sep 2.

Abstract

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 IκBα phosphorylation were increased. Meanwhile, PINK1 overexpression had the opposite effects. In addition, NLRP3 inflammasome overactivation and enhanced p65 and IκBα 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.

Keywords: Bovine mastitis; Mitophagy; NF-κB; NLRP3 inflammasome; S. aureus.

MeSH terms

  • Animals
  • Cattle
  • Epithelial Cells / metabolism
  • Female
  • Inflammasomes / metabolism
  • Mastitis, Bovine*
  • Mitophagy
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • NLR Proteins
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Staphylococcal Infections* / veterinary
  • Staphylococcus aureus / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Inflammasomes
  • NF-kappa B
  • NF-KappaB Inhibitor alpha
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLR Proteins
  • Protein Kinases
  • Ubiquitin-Protein Ligases