Yuko Kawakami1, Tomoaki Ando2, Jong-Rok Lee1, Gisen Kim3, Yu Kawakami1, Tae Nakasaki1, Manando Nakasaki1, Kenji Matsumoto4, Youn Soo Choi5, Toshiaki Kawakami6. 1. Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif. 2. Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif; Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan. 3. Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif. 4. Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. 5. Division of Vaccine Development and Center for Infectious Disease, La Jolla Institute for Allergy and Immunology, La Jolla, Calif. 6. Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, Calif; Laboratory for Allergic Disease, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan. Electronic address: toshi@lji.org.
Abstract
BACKGROUND: Patients with atopic dermatitis (AD) are susceptible to several viruses, including herpes simplex virus (HSV). Some patients experience 1 or more episodes of a severe skin infection caused by HSV termed eczema herpeticum (EH). There are numerous mouse models of AD, but no established model exists for EH. OBJECTIVE: We sought to establish and characterize a mouse model of EH. METHODS: We infected AD-like skin lesions with HSV1 to induce severe skin lesions in a dermatitis-prone mouse strain of NC/Nga. Gene expression was investigated by using a microarray and quantitative PCR; antibody titers were measured by means of ELISA; and natural killer (NK) cell, cytotoxic T-cell, regulatory T-cell, and follicular helper T-cell populations were evaluated by using flow cytometry. The role of NK cells in HSV1-induced development of severe skin lesions was examined by means of depletion and adoptive transfer. RESULTS: Inoculation of HSV1 induced severe erosive skin lesions in eczematous mice, which had an impaired skin barrier, but milder lesions in small numbers of normal mice. Eczematous mice exhibited lower NK cell activity but similar cytotoxic T-cell activity and humoral immune responses compared with normal mice. The role of NK cells in controlling HSV1-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. CONCLUSION: A murine model of EH with an impaired skin barrier was established in this study. We demonstrated a critical role of defective NK activities in the development of HSV1-induced severe skin lesions in eczematous mice.
BACKGROUND:Patients with atopic dermatitis (AD) are susceptible to several viruses, including herpes simplex virus (HSV). Some patients experience 1 or more episodes of a severe skin infection caused by HSV termed eczema herpeticum (EH). There are numerous mouse models of AD, but no established model exists for EH. OBJECTIVE: We sought to establish and characterize a mouse model of EH. METHODS: We infected AD-like skin lesions with HSV1 to induce severe skin lesions in a dermatitis-prone mouse strain of NC/Nga. Gene expression was investigated by using a microarray and quantitative PCR; antibody titers were measured by means of ELISA; and natural killer (NK) cell, cytotoxic T-cell, regulatory T-cell, and follicular helper T-cell populations were evaluated by using flow cytometry. The role of NK cells in HSV1-induced development of severe skin lesions was examined by means of depletion and adoptive transfer. RESULTS: Inoculation of HSV1 induced severe erosive skin lesions in eczematousmice, which had an impaired skin barrier, but milder lesions in small numbers of normal mice. Eczematousmice exhibited lower NK cell activity but similar cytotoxic T-cell activity and humoral immune responses compared with normal mice. The role of NK cells in controlling HSV1-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. CONCLUSION: A murine model of EH with an impaired skin barrier was established in this study. We demonstrated a critical role of defective NK activities in the development of HSV1-induced severe skin lesions in eczematousmice.
Authors: Derek D Sloan; George Zahariadis; Christine M Posavad; Nichlos T Pate; Steven J Kussick; Keith R Jerome Journal: J Immunol Date: 2003-12-15 Impact factor: 5.422