title: Interleukin-1α released from HSV-1-infected keratinocytes acts as a functional alarmin in the skin.
abstract: 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 microinfection 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.
authors.affiliation: Department of Microbiology and Immunology, Temple Autoimmunity Center, Temple University School of Medicine, 1158 MERB, 3500 N Broad Street, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Katelynn A
authors.initials: KA
authors.lastname: Milora
authors.affiliation: Department of Microbiology and Immunology, Temple Autoimmunity Center, Temple University School of Medicine, 1158 MERB, 3500 N Broad Street, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Miller
authors.affiliation: Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, TRL Building, 125 S 31st Street, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Sanmiguel
authors.affiliation: Department of Microbiology and Immunology, Temple Autoimmunity Center, Temple University School of Medicine, 1158 MERB, 3500 N Broad Street, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Liselotte E
authors.initials: LE
authors.lastname: Jensen
mesh_terms: D000067531:Alarmins / Q000378:metabolism*; D000818:Animals; D020169:Caspases / Q000378:metabolism; D002522:Chlorocebus aethiops; D004817:Epidermis / Q000378:metabolism / Q000821:virology; D004847:Epithelial Cells / Q000166:cytology; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D007249:Inflammation; D053582:Interleukin-1alpha / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000821:virology*; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism* / Q000821:virology; D014709:Vero Cells
chemical_list: D000067531:Alarmins; D053582:Interleukin-1alpha; D020169:Caspases