Quick Links

Vaccinia virus inoculation in sites of allergic skin inflammation elicits a vigorous cutaneous IL-17 response.

Authors: Michiko K Oyoshi|||Abdallah Elkhal|||Lalit Kumar|||Jordan E Scott|||Suresh Koduru|||Rui He|||Donald Y M Leung|||Michael D Howell|||Hans C Oettgen|||George F Murphy|||Raif S Geha

Journal: Proceedings of the National Academy of Sciences of the United States of America

Publication Type: Journal Article

Date: 2009

DOI: PMC2736417

ID: 19706451

Affiliations:

Affiliations

    Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.||||||||||||||||||||||||||||||

Abstract

Eczema vaccinatum (EV) is a complication of smallpox vaccination occurring in patients with atopic dermatitis. In affected individuals, vaccinia virus (VV) spreads through the skin, resulting in large primary lesions and satellite lesions, and infects internal organs. BALB/c mice inoculated with VV at sites of Th2-biased allergic skin inflammation elicited by epicutaneous ovalbumin (OVA) sensitization exhibited larger primary lesions that were erosive, more satellite lesions, and higher viral loads in skin and internal organs than mice inoculated in saline-exposed skin, unsensitized skin, or skin sites with Th1-dominant inflammation. VV inoculation in OVA-sensitized skin induced marked local expression of IL-17 transcripts and massive neutrophil infiltration compared to VV inoculation in saline-exposed skin. Treatment with anti-IL-17 decreased the size of primary lesions, numbers of satellite lesions, and viral loads. Addition of IL-17 promoted VV replication in skin explants. These results suggest that IL-17 may be a potential therapeutic target in EV.


Chemical List

    Interleukin-17|||Ovalbumin

Reference List

    Moore ZS, Seward JF, Lane JM. Smallpox. Lancet. 2006;367:425–435.|||Engler RJ, Kenner J, Leung DY. Smallpox vaccination: Risk considerations for patients with atopic dermatitis. J Allergy Clin Immunol. 2002;110:357–365.|||Wollenberg A, Engler R. Smallpox, vaccination and adverse reactions to smallpox vaccine. Curr Opin Allergy Clin Immunol. 2004;4:271–275.|||Sharma DP, Ramsay AJ, Maguire DJ, Rolph MS, Ramshaw IA. Interleukin-4 mediates down regulation of antiviral cytokine expression and cytotoxic T-lymphocyte responses and exacerbates vaccinia virus infection in vivo. J Virol. 1996;70:7103–7107.|||van Den Broek M, et al. IL-4 and IL-10 antagonize IL-12-mediated protection against acute vaccinia virus infection with a limited role of IFN-gamma and nitric oxide synthetase 2. J Immunol. 2000;164:371–378.|||Huang S, et al. Immune response in mice that lack the interferon-gamma receptor. Science. 1993;259:1742–1745.|||Ramirez JC, Tapia E, Esteban M. Administration to mice of a monoclonal antibody that neutralizes the intracellular mature virus form of vaccinia virus limits virus replication efficiently under prophylactic and therapeutic conditions. J Gen Virol. 2002;83:1059–1067.|||Binder D, Kundig TM. Antiviral protection by CD8+ versus CD4+ T cells. CD8+ T cells correlating with cytotoxic activity in vitro are more efficient in antivaccinia virus protection than CD4-dependent IL. J Immunol. 1991;146:4301–4307.|||Kennedy MK, et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med. 2000;191:771–780.|||Howell MD, et al. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity. 2006;24:341–348.|||Toda M, et al. Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol. 2003;111:875–881.|||Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y. Possible pathogenic role of th17 cells for atopic dermatitis. J Invest Dermatol. 2008;128:2625–2630.|||Patera AC, Pesnicak L, Bertin J, Cohen JI. Interleukin 17 modulates the immune response to vaccinia virus infection. Virology. 2002;299:56–63.|||Kohyama S, et al. IL-23 enhances host defense against vaccinia virus infection via a mechanism partly involving IL-17. J Immunol. 2007;179:3917–3925.|||Spergel JM, et al. Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest. 1998;101:1614–1622.|||He R, Oyoshi MK, Jin H, Geha RS. Epicutaneous antigen exposure induces a Th17 response that drives airway inflammation after inhalation challenge. Proc Natl Acad Sci USA. 2007;104:15817–15822.|||Spergel JM, Mizoguchi E, Oettgen H, Bhan AK, Geha RS. Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Invest. 1999;103:1103–1111.|||Effendy I, Loffler H, Maibach HI. Epidermal cytokines in murine cutaneous irritant responses. J Appl Toxicol. 2000;20:335–341.|||Scott JE, et al. Impaired immune response to vaccinia virus inoculated at the site of cutaneous allergic inflammation. J Allergy Clin Immunol. 2007;120:1382–1388.|||Ye P, et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J Exp Med. 2001;194:519–527.|||Prause O, Laan M, Lotvall J, Linden A. Pharmacological modulation of interleukin-17-induced GCP-2-, GRO-alpha- and interleukin-8 release in human bronchial epithelial cells. Eur J Pharmacol. 2003;462:193–198.|||Schnyder-Candrian S, et al. Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med. 2006;203:2715–2725.|||Amegadzie BY, Ahn BY, Moss B. Identification, sequence, and expression of the gene encoding a Mr 35,000 subunit of the vaccinia virus DNA-dependent RNA polymerase. J Biol Chem. 1991;266:13712–13718.|||Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of T(H)17 cells. Nature. 2008;453:1051–1057.|||Hou W, Kang HS, Kim BS. Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection. J Exp Med. 2009;206:313–328.|||Antonysamy MA, et al. Evidence for a role of IL-17 in organ allograft rejection: IL-17 promotes the functional differentiation of dendritic cell progenitors. J Immunol. 1999;162:577–584.