Exploring mechanisms of Interleukin-1α release from HSV-1 infected keratinocytes during active skin infection (INM6P.340)

Abstract

Abstract IL-1 cytokines, IL-1α and IL-1β, have been widely studied in a variety of disease models. These molecules are mostly known for their inflammatory properties; however, they have been shown to have pleiotropic effects under diverse circumstances and within different cell types. Recently, the herpes simplex virus-1 (HSV-1) was shown to inhibit IL-1β release during infection and consequently possibly blocking IL-1β dependent immune responses. We previously demonstrated that IL-1α is expressed and released from cells exposed to bacteria. Utilizing a mouse model of HSV-1 skin infection, we recently further showed that an intracellular store of preformed IL-1α is released from keratinocytes soon after infection, independent of inflammatory caspase activation. IL-1α signaling through its receptor, IL-1R1, was subsequently responsible for leukocyte recruitment to infected epidermal cells. This showed, for the first time, this cytokine’s ability to act as an alarmin during cutaneous viral infection. Consequently, IL-1R1 knockout mice had an increased mortality rate compared to wild type mice due to viral dissemination. Recent studies have aimed to evaluate mechanisms whereby IL-1α is released from infected keratinocytes and discover potential proteins involved. These experiments will help to elucidate the role of IL-1α during viral infection while furthering our understanding of IL-1 signaling mechanisms.