Toll-Like Receptor 2 and Lipoprotein-Like Lipoproteins Enhance Staphylococcus aureus Invasion in Epithelial Cells

Infect Immun. 2018 Jul 23;86(8):e00343-18. doi: 10.1128/IAI.00343-18. Print 2018 Aug.

Abstract

Staphylococcus aureus contains a certain subclass of lipoproteins, the so-called lipoprotein-like lipoproteins (Lpl's), that not only represent Toll-like receptor 2 (TLR2) ligands but are also involved in host cell invasion. Here we addressed the question of which factors contribute to Lpl-mediated invasion of epithelial cells and keratinocytes. For this purpose, we compared the invasiveness of USA300 and its Δlpl mutant under different conditions. In the presence of the matrix proteins IgG, fibrinogen (Fg), and fibronectin (Fn), and of fetal bovine serum (FBS), the invasion ratio was increased in both strains, and always more in USA300 than in its Δlpl mutant. Interestingly, when we compared the invasion of HEK-0 and HEK-TLR2 cells, the cells expressing TLR2 showed a 9-times-higher invasion frequency. When HEK-TLR2 cells were additionally stimulated with a synthetic lipopeptide, Pam3CSK4 (P3C), the invasion frequency was further increased. A potential reason for the positive effect of TLR2 on invasion could be that TLR2 activation by P3C also activates F-actin formation. Here we show that S. aureus invasion depends on a number of factors, on the host side as well as on the bacterial side.

Keywords: HEK293; HaCaT; Lpl; Staphylococcus aureus; TLR2; host cell invasion; invasion; lipoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Bacterial Proteins / metabolism*
  • Cell Line
  • Endocytosis*
  • Epithelial Cells / microbiology*
  • Gene Deletion
  • Host-Pathogen Interactions*
  • Humans
  • Keratinocytes / microbiology
  • Lipoproteins / genetics
  • Lipoproteins / metabolism*
  • Staphylococcus aureus / pathogenicity*
  • Toll-Like Receptor 2 / metabolism*

Substances

  • Actins
  • Bacterial Proteins
  • Lipoproteins
  • Toll-Like Receptor 2