Dataset Information

Staphylococcus aureus ?-toxin modulates skin host response to viral infection.

ABSTRACT:

Background

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.

Objective

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.

Methods

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 ?-toxin, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 protein and ?-toxin heptamers were detected by using Western blot assays.

Results

We demonstrate that sublytic staphylococcal ?-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 ?-toxin-producing S aureus strain compared with murine skin inoculated with the isogenic ?-toxin-deleted strain. The viral enhancing effect of ?-toxin is mediated by ADAM10 and is associated with its pore-forming property. Moreover, we demonstrate that ?-toxin promotes viral entry in NHKs.

Conclusion

The current study introduces the novel concept that staphylococcal ?-toxin promotes viral skin infection and provides a mechanism by which S aureus infection might predispose the host toward disseminated viral infections.

SUBMITTER: Bin L

PROVIDER: S-EPMC3594992 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

Staphylococcus aureus α-toxin modulates skin host response to viral infection.

Bin Lianghua L Kim Byung Eui BE Brauweiler Anne A Goleva Elena E Streib Joanne J Ji Yinduo Y Schlievert Patrick M PM Leung Donald Y M DY

The Journal of allergy and clinical immunology 20120726 3

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>NHKs were ...[more]

PMID: 22840852

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