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

Lianghua Bin, Byung Eui Kim, Anne Brauweiler, Elena Goleva, Joanne Streib, Yinduo Ji, Patrick M. Schlievert, Donald Y.M. Leung

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)683-691.e2
JournalJournal of Allergy and Clinical Immunology
Volume130
Issue number3
DOIs
StatePublished - Sep 2012

Bibliographical note

Funding Information:
Supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases Atopic Dermatitis Research Network contract HHSN272201000020C and R01 AR41256 .

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • Atopic dermatitis
  • Staphylococcus aureus
  • a disintegrin and metalloprotease 10
  • herpes simplex virus
  • vaccinia virus
  • α-toxin

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