Staphylococcus aureus α-toxin modulates skin host response to viral infection
| Autor: | Patrick M. Schlievert, Byung Eui Kim, Donald Y.M. Leung, Joanne E. Streib, Yinduo Ji, Elena Goleva, Lianghua Bin, Anne Brauweiler |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Keratinocytes
viruses Immunology Bacterial Toxins Herpesvirus 1 Human Biology medicine.disease_cause Virus Replication Eczema vaccinatum Virus Article Microbiology ADAM10 Protein Hemolysin Proteins Mice Multiplicity of infection Viral entry medicine Immunology and Allergy Animals Humans Cells Cultured Skin Mice Inbred BALB C Superantigens Membrane Proteins Viral Load medicine.disease Virology ADAM Proteins Herpes simplex virus Viral replication Staphylococcus aureus DNA Viral Skin Diseases Viral Female Amyloid Precursor Protein Secretases Viral load |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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