Streptococcus pneumoniae DNA Initiates Type I Interferon Signaling in the Respiratory Tract
Authors
Parker, DaneMartin, Francis J.
Soong, Grace
Harfenist, Bryan S.
Aguilar, Jorge L.
Ratner, Adam J.
Fitzgerald, Katherine A.
Schindler, Christian
Prince, Alice
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2011-05-19Keywords
Interferon Type IStreptococcus pneumoniae
Immunity, Mucosal
Mucous Membrane
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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-beta 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-alpha/beta 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. IMPORTANCE: The bacterium Streptococcus pneumoniae is a leading cause of bacterial pneumonia, leading to upwards of one million deaths a year worldwide and significant economic burden. Although it is known that antibody is critical for efficient phagocytosis, it is not known how this pathogen is sensed by the mucosal epithelium. We demonstrate that this extracellular pathogen activates mucosal signaling typically activated by viral pathogens via the pneumolysin pore to activate intracellular receptors and the type I interferon (IFN) cascade. Mice lacking the receptor to type I IFNs have a reduced ability to clear S. pneumoniae, suggesting that the type I IFN cascade is central to the mucosal clearance of this important pathogen.Source
Parker D, et al. 2011. Streptococcus pneumoniae DNA initiates type I interferon signaling in the respiratory tract. mBio 2(3):e00016-11. doi:10.1128/mBio.00016-11. Link to article on publisher's siteDOI
10.1128/mBio.00016-11Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34902PubMed ID
21586648Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/mBio.00016-11