Staphylococcus aureus Phenol-Soluble Modulins Impair Interleukin Expression in Bovine Mammary Epithelial Cells

Infect Immun. 2016 May 24;84(6):1682-1692. doi: 10.1128/IAI.01330-15. Print 2016 Jun.

Abstract

The role of the recently described interleukin-32 (IL-32) in Staphylococcus aureus-induced mastitis, an inflammation of the mammary gland, is unclear. We determined expression of IL-32, IL-6, and IL-8 in S. aureus- and Escherichia coli-infected bovine mammary gland epithelial cells. Using live bacteria, we found that in S. aureus-infected cells, induction of IL-6 and IL-8 expression was less pronounced than in E. coli-infected cells. Notably, IL-32 expression was decreased in S. aureus-infected cells, while it was increased in E. coli-infected cells. We identified the staphylococcal phenol-soluble modulin (PSM) peptides as key contributors to these effects, as IL-32, IL-6, and IL-8 expression by epithelial cells exposed to psm mutant strains was significantly increased compared to that in cells exposed to the isogenic S. aureus wild-type strain, indicating that PSMs inhibit the production of these interleukins. The use of genetically complemented strains confirmed this observation. Inasmuch as the decreased expression of IL-32, which is involved in dendritic cell maturation, impairs immune responses, our results support a PSM-dependent mechanism that allows for the development of chronic S. aureus-related mastitis.

MeSH terms

  • Animals
  • Bacterial Toxins / biosynthesis*
  • Bacterial Toxins / genetics
  • Bacterial Toxins / toxicity
  • Cattle
  • Cell Line
  • Epithelial Cells / drug effects
  • Epithelial Cells / microbiology*
  • Epithelial Cells / pathology
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Female
  • Gene Expression Regulation
  • Genetic Complementation Test
  • Host-Pathogen Interactions*
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Interleukins / genetics*
  • Interleukins / immunology
  • Mammary Glands, Animal / immunology
  • Mammary Glands, Animal / pathology
  • Signal Transduction
  • Species Specificity
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / pathogenicity*
  • Virulence

Substances

  • Bacterial Toxins
  • Interleukin-6
  • Interleukin-8
  • Interleukins
  • staphylococcal delta toxin