The Alarmin IL-33 Derived from HSV-2-Infected Keratinocytes Triggers Mast Cell- Mediated Antiviral Innate Immunity  Rui Aoki, Tatsuyoshi Kawamura, Fumi Goshima, Youichi Ogawa, Susumu Nakae, Kohji Moriishi, Atsuhito Nakao, Shinji Shimada  Journal of Investigative Dermatology  Volume 136, Issue 6, Pages 1290-1292 (June 2016) DOI: 10.1016/j.jid.2016.01.030 Copyright © 2016 The Authors Terms and Conditions

Figure 1 Functional IL-33 expression and production by HSV-2-infected keratinocytes. (a) Kinetic analysis of tissue levels of IL-33 and HSV-2 titer in the skin lysates of WT (B6) mice (n = 3) after HSV-2 infection at indicated time points. (b) Immunohistochemical staining for IL-33 in skin of WT mice at day 1 after intradermal infection with HSV-2. Original magnification ×200. Size bars = 100 μm. (c) BMMCs were stimulated with culture supernatants of lesional epidermal sheets obtained from WT (B6) mice (n = 3) or IL-33−/− mice (n = 3) intradermally injected with HSV-2, and analyzed for TNF-α production by ELISA. *P < 0.05 versus results for BMMCs treated with HSV-2-infected epidermis sup from IL-33−/− mice. **P < 0.01 versus results for BMMCs treated with uninfected epidermis sup from WT mice. BMMCs, bone marrow-derived mast cells; HSV-2, herpes simplex virus-2; TNF-α, tumor necrosis factor- α; WT, wild-type. Journal of Investigative Dermatology 2016 136, 1290-1292DOI: (10.1016/j.jid.2016.01.030) Copyright © 2016 The Authors Terms and Conditions

Figure 2 IL-33/ST2 signaling contributes to anti-HSV-2 host defense in vivo. Survival rates, clinical (EAE) scores, and lesion scores of WT (B6) mice and ST2−/− mice (a), or KitW/W-v mice, Kit+/+ mice, WT BMMC-reconstituted KitW/W-v mice, and ST2−/− BMMC-reconstituted KitW/W-v mice (b) at the indicated time points after intradermal injection with HSV-2 are shown. *P < 0.05 and **P < 0.01 versus WT mice (a) or KitW/W-v mice (b). Data are representative of at least two independent experiments; n = 7–10 mice/group. BMMCs, bone marrow-derived mast cells; EAE, experimental autoimmune encephalomyelitis; HSV-2, herpes simplex virus-2; WT, wild-type. Journal of Investigative Dermatology 2016 136, 1290-1292DOI: (10.1016/j.jid.2016.01.030) Copyright © 2016 The Authors Terms and Conditions