Bovine neutrophils stimulated with Streptococcus uberis induce neutrophil extracellular traps, and cause cytotoxicity and transcriptional upregulation of inflammatory cytokine genes in bovine mammary epithelial cells

J Vet Med Sci. 2024 Feb 8;86(2):141-149. doi: 10.1292/jvms.23-0302. Epub 2023 Dec 18.

Abstract

This study aimed to understand the response of neutrophils stimulated by Streptococcus uberis, a major cause of mastitis. It was found that the production of neutrophil extracellular traps (NETs) was induced in milk clots from mastitic milk produced by S. uberis-infected bovine udders. The release of NETs from neutrophils stimulated by S. uberis was investigated. Bovine neutrophils cocultured with S. uberis in vitro released the components of NETs, which contained extracellular DNA and elastase. Bovine mammary epithelial cells (BMECs) incubated in coculture supernatants containing components of NETs, caused cytotoxicity and transcriptional upregulation of inflammatory cytokines, including of interleukin (IL) -1β, tumor necrosis factor (TNF)-α, IL-6, and IL-8, in BMECs. These findings suggest that bovine neutrophils stimulated by S. uberis induce responses that cause exacerbated inflammation, such as NET formation, cytotoxicity against BMECs, and increased production of inflammatory cytokines. Bovine neutrophil responses stimulated by S. uberis could be involved in the progression of S. uberis-induced mastitis.

Keywords: Streptococcus uberis; bovine neutrophil; inflammation; mastitis; neutrophil extracellular trap.

MeSH terms

  • Animals
  • Cattle
  • Cattle Diseases* / pathology
  • Cytokines / genetics
  • Epithelial Cells / metabolism
  • Extracellular Traps* / metabolism
  • Female
  • Interleukin-1beta
  • Mammary Glands, Animal / pathology
  • Mastitis, Bovine*
  • Neutrophils / metabolism
  • Streptococcal Infections* / pathology
  • Streptococcal Infections* / veterinary
  • Streptococcus*
  • Tumor Necrosis Factor-alpha / genetics
  • Up-Regulation

Substances

  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-1beta

Supplementary concepts

  • Streptococcus uberis