The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2 (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation

P Müller, M Müller-Anstett, J Wagener, Q Gao, S Kaesler, M Schaller, T Biedermann, F Götz

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Abstract

SitC is one of the predominant lipoproteins in Staphylococcus aureus. Recently, SitC was shown to be capable of stimulating Toll-like receptor 2 (TLR2), but the mechanism of TLR2 activation by SitC has not been analyzed in detail so far. In this study, we purified C-terminally His-tagged SitC (SitC-His) from Staphylococcus aureus. SitC-His induced interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) release in human monocytes and also NF-¿B activation in TLR2-transfected HEK293 cells, indicating TLR2-specific activation. SitC not only induced a TLR2-dependent release of IL-6 in primary murine keratinocytes (MKs) but also induced intracellular accumulation of TLR2, which was time and concentration dependent. Cy2-labeled SitC-His colocalized specifically with TLR2 in MKs and was also internalized in TLR2 knockout MKs, suggesting a TLR2-independent uptake. Neither activation nor colocalization of SitC-His was observed with TLR4 or Nod2. The results show that the native lipoprotein SitC-His specifically colocalizes with TLR2, is internalized by host cells, induces proinflammatory cytokines, and triggers intracellular accumulation of TLR2.
Original languageEnglish
Pages (from-to)4243-4250
Number of pages8
JournalInfection and Immunity
Volume78
Issue number10
DOIs
Publication statusPublished - Oct 2010

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Keywords

  • animals
  • bacterial proteins
  • cell line
  • cytokines
  • gene expression regulation, bacterial
  • humans
  • keratinocytes
  • lipoproteins
  • mice
  • mice, inbred C57BL
  • mice, knockout
  • Nod2 signaling adaptor protein
  • protein transport
  • specific pathogen-free organisms
  • Staphylococcus aureus
  • toll-like receptor 2

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