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Streptococcus pneumoniae DNA Initiates Type I Interferon Signaling in the Respiratory Tract

By Dane Parker, Francis J. Martin, Grace Soong, Bryan S. Harfenist, Jorge L. Aguilar, Adam J. Ratner, Katherine A. Fitzgerald, Christian Schindler and Alice Prince

Abstract

The mucosal epithelium is the initial target for respiratory pathogens of all types. While type I interferon (IFN) signaling is traditionally associated with antiviral immunity, we demonstrate that the extracellular bacterial pathogen Streptococcus pneumoniae activates the type I IFN cascade in airway epithelial and dendritic cells. This response is dependent upon the pore-forming toxin pneumolysin. Pneumococcal DNA activates IFN-β expression through a DAI/STING/TBK1/IRF3 cascade. Tlr4−/−, Myd88−/−, Trif−/−, and Nod2−/− mutant mice had no impairment of type I IFN signaling. Induction of type I IFN signaling contributes to the eradication of pneumococcal carriage, as IFN-α/β receptor null mice had significantly increased nasal colonization with S. pneumoniae compared with that of wild-type mice. These studies suggest that the type I IFN cascade is a central component of the mucosal response to airway bacterial pathogens and is responsive to bacterial pathogen-associated molecular patterns that are capable of accessing intracellular receptors

Topics: Research Article
Publisher: American Society of Microbiology
OAI identifier: oai:pubmedcentral.nih.gov:3101776
Provided by: PubMed Central

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