RGD Reference Report - Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A. - Rat Genome Database

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

Authors: Martin, FJ  Gomez, MI  Wetzel, DM  Memmi, G  O'Seaghdha, M  Soong, G  Schindler, C  Prince, A 
Citation: Martin FJ, etal., J Clin Invest. 2009 Jul;119(7):1931-9.
RGD ID: 5490273
Pubmed: PMID:19603548   (View Abstract at PubMed)
PMCID: PMC2701857   (View Article at PubMed Central)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Staphylococcal Pneumonia  ISOIfnar1 (Mus musculus)5490273; 5490273 RGD 
Staphylococcal Pneumonia susceptibilityIMP 5490273 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ifnar1  (interferon alpha and beta receptor subunit 1)

Genes (Mus musculus)
Ifnar1  (interferon (alpha and beta) receptor 1)

Genes (Homo sapiens)
IFNAR1  (interferon alpha and beta receptor subunit 1)


Additional Information