Interleukin-1α released from HSV-1-infected keratinocytes acts as a functional alarmin in the skin
| Autor: | Samantha L. Miller, Liselotte E. Jensen, Julio Sanmiguel, Katelynn A. Milora |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Keratinocytes
viruses General Physics and Astronomy Inflammation Herpesvirus 1 Human General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice 0302 clinical medicine Immune system Interleukin-1alpha Chlorocebus aethiops Extracellular medicine Leukocytes Alarmins Animals Humans Vero Cells Caspase 030304 developmental biology Skin Mice Knockout 0303 health sciences Multidisciplinary biology Epidermis (botany) Epithelial Cells Herpes Simplex General Chemistry 3. Good health Mice Inbred C57BL 030220 oncology & carcinogenesis Caspases Immune System Immunology biology.protein Vero cell medicine.symptom Signal transduction Epidermis Intracellular Signal Transduction |
| Zdroj: | Nature communications |
| ISSN: | 2041-1723 |
| Popis: | Herpes simplex virus-1 (HSV-1) is a human pathogen that utilizes several strategies to circumvent the host immune response. An immune evasion mechanism employed by HSV-1 is retention of interleukin-1β (IL-1β) in the intracellular space, which blocks the pro-inflammatory activity of IL-1β. Here, we report that HSV-1 infected keratinocytes actively release the also pro-inflammatory IL-1α, preserving the ability of infected cells to signal danger to the surrounding tissue. The extracellular release of IL-1α is independent of inflammatory caspases. In vivo recruitment of leukocytes to early HSV-1 micro-infection sites within the epidermis is dependent upon IL-1 signalling. Following cutaneous HSV-1 infection, mice unable to signal via extracellular IL-1α exhibit an increased mortality rate associated with viral dissemination. We conclude that IL-1α acts as an alarmin essential for leukocyte recruitment and protective immunity against HSV-1. This function may have evolved to counteract an immune evasion mechanism deployed by HSV-1. |
| Databáze: | OpenAIRE |
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