Journal article
Staphylococcus aureus α-toxin modulates skin host response to viral infection
Journal of allergy and clinical immunology, Vol.130(3), pp.683-691.e2
09/2012
DOI: 10.1016/j.jaci.2012.06.019
PMCID: PMC3594992
PMID: 22840852
Abstract
Patients with atopic dermatitis (AD) with a history of eczema herpeticum have increased staphylococcal colonization and infections. However, whether Staphylococcus aureus alters the outcome of skin viral infection has not been determined.
We investigated whether S aureus toxins modulated host response to herpes simplex virus (HSV) 1 and vaccinia virus (VV) infections in normal human keratinocytes (NHKs) and in murine infection models.
NHKs were treated with S aureus toxins before incubation of viruses. BALB/c mice were inoculated with S aureus 2 days before VV scarification. Viral loads of HSV-1 and VV were evaluated by using real-time PCR, a viral plaque-forming assay, and immunofluorescence staining. Small interfering RNA duplexes were used to knockdown the gene expression of the cellular receptor of α-toxin, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 protein and α-toxin heptamers were detected by using Western blot assays.
We demonstrate that sublytic staphylococcal α-toxin increases viral loads of HSV-1 and VV in NHKs. Furthermore, we demonstrate in vivo that the VV load is significantly greater (P < .05) in murine skin inoculated with an α-toxin–producing S aureus strain compared with murine skin inoculated with the isogenic α-toxin–deleted strain. The viral enhancing effect of α-toxin is mediated by ADAM10 and is associated with its pore-forming property. Moreover, we demonstrate that α-toxin promotes viral entry in NHKs.
The current study introduces the novel concept that staphylococcal α-toxin promotes viral skin infection and provides a mechanism by which S aureus infection might predispose the host toward disseminated viral infections.
Details
- Title: Subtitle
- Staphylococcus aureus α-toxin modulates skin host response to viral infection
- Creators
- Lianghua Bin - Department of Pediatrics, National Jewish Health, Denver, ColoByung Eui Kim - Department of Pediatrics, National Jewish Health, Denver, ColoAnne Brauweiler - Department of Pediatrics, National Jewish Health, Denver, ColoElena Goleva - Department of Pediatrics, National Jewish Health, Denver, ColoJoanne Streib - Department of Pediatrics, National Jewish Health, Denver, ColoYinduo Ji - Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MinnPatrick M Schlievert - Department of Microbiology, University of Iowa, Iowa City, IowaDonald Y.M Leung - Department of Pediatrics, National Jewish Health, Denver, Colo
- Resource Type
- Journal article
- Publication Details
- Journal of allergy and clinical immunology, Vol.130(3), pp.683-691.e2
- Publisher
- Mosby, Inc
- DOI
- 10.1016/j.jaci.2012.06.019
- PMID
- 22840852
- PMCID
- PMC3594992
- ISSN
- 0091-6749
- eISSN
- 1097-6825
- Grant note
- HHSN272201000020C; R01 AR41256 / National Institutes of Health/National Institute of Allergy and Infectious Diseases Atopic Dermatitis Research Network
- Language
- English
- Date published
- 09/2012
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001151902771
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