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Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A

Martin, F. J. and Gomez, M. I. and Wetzel, D. M. and Memmi, G. and O'Seaghdha M., and Soong, G. and Schindler, C. and Prince, A.. (2009) Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A. Journal of Clinical Investigation, Vol. 119, H. 7. S. 1931-1939.

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Official URL: http://edoc.unibas.ch/dok/A5843332

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Abstract

The activation of type I IFN signaling is a major component of host defense against viral infection, but it is not typically associated with immune responses to extracellular bacterial pathogens. Using mouse and human airway epithelial cells, we have demonstrated that Staphylococcus aureus activates type I IFN signaling, which contributes to its virulence as a respiratory pathogen. This response was dependent on the expression of protein A and, more specifically, the Xr domain, a short sequence-repeat region encoded by DNA that consists of repeated 24-bp sequences that are the basis of an internationally used epidemiological typing scheme. Protein A was endocytosed by airway epithelial cells and subsequently induced IFN-beta expression, JAK-STAT signaling, and IL-6 production. Mice lacking IFN-alpha/beta receptor 1 (IFNAR-deficient mice), which are incapable of responding to type I IFNs, were substantially protected against lethal S. aureus pneumonia compared with wild-type control mice. The profound immunological consequences of IFN-beta signaling, particularly in the lung, may help to explain the conservation of multiple copies of the Xr domain of protein A in S. aureus strains and the importance of protein A as a virulence factor in the pathogenesis of staphylococcal pneumonia
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Environmental Exposures and Health > Physical Hazards and Health (Röösli)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Health Systems Research and Dynamic Modelling > Dynamical Modelling (Smith)
UniBasel Contributors:Schindler, Christian
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:American Society for Clinical Investigation
ISSN:0021-9738
e-ISSN:1558-8238
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Oct 2017 08:20
Deposited On:14 Sep 2012 06:43

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