The TLR2 Antagonist Staphylococcal Superantigen-Like Protein 3 Acts as a Virulence Factor to Promote Bacterial Pathogenicity in vivo

Kirsten J. Koymans*, Oliver Goldmann, Christofer A.Q. Karlsson, Wiedjai Sital, Robert Thänert, Adinda Bisschop, Manouk Vrieling, Johan Malmström, Kok P.M. Van Kessel, Carla J.C. De Haas, Jos A.G. Van Strijp, Eva Medina

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)

Abstract

Toll-like receptor (TLR) signaling is important in the initiation of immune responses and subsequent instigation of adaptive immunity. TLR2 recognizes bacterial lipoproteins and plays a central role in the host defense against bacterial infections, including those caused by Staphylococcus aureus. Many studies have demonstrated the importance of TLR2 in murine S. aureus infection. S. aureus evades TLR2 activation by secreting two proteins, staphylococcal superantigen-like protein 3 (SSL3) and 4 (SSL4). In this study, we demonstrate that antibodies against SSL3 and SSL4 are found in healthy individuals, indicating that humans are exposed to these proteins during S. aureus colonization or infection. To investigate the TLR2-antagonistic properties of SSL3 and SSL4, we compared the infection with wild-type and SSL3/4 knockout S. aureus strains in an intravenous murine infection model. Direct evaluation of the contribution of SSL3/4 to infection pathogenesis was hindered by the fact that the SSLs were not expressed in the murine system. To circumvent this limitation, an SSL3-overproducing strain (pLukM-SSL3) was generated, resulting in constitutive expression of SSL3. pLukM-SSL3 exhibited increased virulence compared to the parental strain in a murine model that was found to be TLR2 dependent. Altogether, these data indicate that SSL3 contributes to S. aureus virulence in vivo.

Original languageEnglish
Pages (from-to)561-573
Number of pages13
JournalJournal of Innate Immunity
Volume9
Issue number6
DOIs
Publication statusPublished - 1 Nov 2017
Externally publishedYes

Keywords

  • Immune evasion
  • Innate immunity
  • Staphylococcal superantigen-like protein 3
  • Staphylococcus aureus
  • TLR2 antagonist
  • Toll-like receptor 2

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