Staphylococcus aureus induces type I IFN signaling in dendritic cells via TLR9

Dane Parker, Alice Prince

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

The importance of type I IFN signaling in the innate immune response to viral and intracellular pathogens is well established, with an increasing literature implicating extracellular bacterial pathogens, including Staphylococcus aureus, in this signaling pathway. Airway epithelial cells and especially dendritic cells (DCs) contribute to the production of type I IFNs in the lung. We were interested in establishing how S. aureus activates the type I IFN cascade in DCs. In vitro studies confirmed the rapid uptake of S. aureus by DCs followed promptly by STAT1 phosphorylation and expression of IFN-β. Signaling occurred using heat-killed organisms and in the absence of PVL and α-toxin. Consistent with the participation of endosomal and not cytosolic receptors, signaling was predominantly mediated by MyD88, TLR9, and IRF1 and blocked by cytochalasin D, dynasore, and chloroquine. To determine the role of TLR9 signaling in the pathogenesis of S. aureus pneumonia, we infected WT and Tlr9-/- mice with MRSA USA300. Tlr9-/- mice had significantly improved clearance of S. aureus from the airways and lung tissue. Ifnar-/- mice also had improved clearance. This enhanced clearance in Tlr9-/- mice was not due to differences in the numbers of recruited neutrophils into the airways, but instead correlated with decreased induction of TNF. Thus, we identified TLR9 as the critical receptor mediating the induction of type I IFN signaling in DCs in response to S. aureus, illustrating an additional mechanism through which S. aureus exploits innate immune signaling to facilitate infection.

Original languageEnglish (US)
Pages (from-to)4040-4046
Number of pages7
JournalJournal of Immunology
Volume189
Issue number8
DOIs
StatePublished - Oct 15 2012

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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