Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum
Threats of bioterrorism have renewed efforts to better understand poxvirus pathogenesis and to develop a safer vaccine against smallpox. Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (...
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| Veröffentlicht in: | The Journal of experimental medicine 2009-06, Vol.206 (6), p.1219-1225 |
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| container_title | The Journal of experimental medicine |
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| creator | Kawakami, Yuko Tomimori, Yoshiaki Yumoto, Kenji Hasegawa, Shunji Ando, Tomoaki Tagaya, Yutaka Crotty, Shane Kawakami, Toshiaki |
| description | Threats of bioterrorism have renewed efforts to better understand poxvirus pathogenesis and to develop a safer vaccine against smallpox. Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (VACV) infection. To study the underlying mechanism of the vulnerability of atopic dermatitis patients to VACV infection, we developed a mouse model of eczema vaccinatum. Virus infection of eczematous skin induced severe primary erosive skin lesions, but not in the skin of healthy mice. Eczematous mice exhibited lower natural killer (NK) cell activity but similar cytotoxic T lymphocyte activity and humoral immune responses. The role of NK cells in controlling VACV-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. The proinflammatory cytokine interleukin (IL)-17 reduced NK cell activity in mice with preexisting dermatitis. Given low NK cell activities and increased IL-17 expression in atopic dermatitis patients, these results can explain the increased susceptibility of atopic dermatitis patients to eczema vaccinatum. |
| doi_str_mv | 10.1084/jem.20082835 |
| format | Article |
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Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (VACV) infection. To study the underlying mechanism of the vulnerability of atopic dermatitis patients to VACV infection, we developed a mouse model of eczema vaccinatum. Virus infection of eczematous skin induced severe primary erosive skin lesions, but not in the skin of healthy mice. Eczematous mice exhibited lower natural killer (NK) cell activity but similar cytotoxic T lymphocyte activity and humoral immune responses. The role of NK cells in controlling VACV-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. The proinflammatory cytokine interleukin (IL)-17 reduced NK cell activity in mice with preexisting dermatitis. Given low NK cell activities and increased IL-17 expression in atopic dermatitis patients, these results can explain the increased susceptibility of atopic dermatitis patients to eczema vaccinatum.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20082835</identifier><identifier>PMID: 19468065</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Animals ; Brief Definitive Report ; Cells, Cultured ; Dermatitis, Atopic - immunology ; Dermatitis, Atopic - pathology ; Disease Models, Animal ; Disease Susceptibility - immunology ; Disease Susceptibility - virology ; Humans ; Interleukin-17 - genetics ; Interleukin-17 - immunology ; Kaposi Varicelliform Eruption - immunology ; Kaposi Varicelliform Eruption - pathology ; Kaposi Varicelliform Eruption - virology ; Killer Cells, Natural - cytology ; Killer Cells, Natural - immunology ; Mice ; Poxvirus ; Skin - immunology ; Skin - pathology ; Skin - virology ; Smallpox - immunology ; Vaccinia virus ; Vaccinia virus - immunology</subject><ispartof>The Journal of experimental medicine, 2009-06, Vol.206 (6), p.1219-1225</ispartof><rights>2009 Kawakami et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-288ce4a06c7b6cf6cf5167d38708531bf0a640c08a474e4b4e5b241bc52a46d43</citedby><cites>FETCH-LOGICAL-c479t-288ce4a06c7b6cf6cf5167d38708531bf0a640c08a474e4b4e5b241bc52a46d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19468065$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawakami, Yuko</creatorcontrib><creatorcontrib>Tomimori, Yoshiaki</creatorcontrib><creatorcontrib>Yumoto, Kenji</creatorcontrib><creatorcontrib>Hasegawa, Shunji</creatorcontrib><creatorcontrib>Ando, Tomoaki</creatorcontrib><creatorcontrib>Tagaya, Yutaka</creatorcontrib><creatorcontrib>Crotty, Shane</creatorcontrib><creatorcontrib>Kawakami, Toshiaki</creatorcontrib><title>Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Threats of bioterrorism have renewed efforts to better understand poxvirus pathogenesis and to develop a safer vaccine against smallpox. Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (VACV) infection. To study the underlying mechanism of the vulnerability of atopic dermatitis patients to VACV infection, we developed a mouse model of eczema vaccinatum. Virus infection of eczematous skin induced severe primary erosive skin lesions, but not in the skin of healthy mice. Eczematous mice exhibited lower natural killer (NK) cell activity but similar cytotoxic T lymphocyte activity and humoral immune responses. The role of NK cells in controlling VACV-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. The proinflammatory cytokine interleukin (IL)-17 reduced NK cell activity in mice with preexisting dermatitis. Given low NK cell activities and increased IL-17 expression in atopic dermatitis patients, these results can explain the increased susceptibility of atopic dermatitis patients to eczema vaccinatum.</description><subject>Animals</subject><subject>Brief Definitive Report</subject><subject>Cells, Cultured</subject><subject>Dermatitis, Atopic - immunology</subject><subject>Dermatitis, Atopic - pathology</subject><subject>Disease Models, Animal</subject><subject>Disease Susceptibility - immunology</subject><subject>Disease Susceptibility - virology</subject><subject>Humans</subject><subject>Interleukin-17 - genetics</subject><subject>Interleukin-17 - immunology</subject><subject>Kaposi Varicelliform Eruption - immunology</subject><subject>Kaposi Varicelliform Eruption - pathology</subject><subject>Kaposi Varicelliform Eruption - virology</subject><subject>Killer Cells, Natural - cytology</subject><subject>Killer Cells, Natural - immunology</subject><subject>Mice</subject><subject>Poxvirus</subject><subject>Skin - immunology</subject><subject>Skin - pathology</subject><subject>Skin - virology</subject><subject>Smallpox - immunology</subject><subject>Vaccinia virus</subject><subject>Vaccinia virus - immunology</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1P3DAQhq2qqGyht56RTz01MHb8lUulCpV21RVc4Gw5zqSYJjHESartjX-OV2y_TpUsz2FePZ7xQ8hbBqcMjDi7w_6UAxhuSvmCrJgUUFSyNC_JCoDzggHoQ_I6pTsAJoRUr8ghq4QyoOSKPK6H21CHKcSBxpZefqUeu446P4UlTFtab-l6UzBNXdfFH4kuzvswBEeXMM6JTpGGoZk90oQLjrl8DwPtMGVeyi3qaB_nhPlusNu9gP4n9m7PcdPcH5OD1nUJ3-zrEbm5-HR9_qXYXH1en3_cFF7oaiq4MR6FA-V1rXybj2RKN6XRYGTJ6hacEuDBOKEFilqgrLlgtZfcCdWI8oh8eObez3WPjcdhGl1n78fQu3Frowv2384Qbu23uFiumQTJM-DdHjDGhxnTZPuQdr_lBsw7WqXLsqqY-W-QZw3aVLuR3j8H_RhTGrH9PQ0Du5Nrs1z7S26On_y9wZ_w3mb5BB8FoZ4</recordid><startdate>20090608</startdate><enddate>20090608</enddate><creator>Kawakami, Yuko</creator><creator>Tomimori, Yoshiaki</creator><creator>Yumoto, Kenji</creator><creator>Hasegawa, Shunji</creator><creator>Ando, Tomoaki</creator><creator>Tagaya, Yutaka</creator><creator>Crotty, Shane</creator><creator>Kawakami, Toshiaki</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090608</creationdate><title>Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum</title><author>Kawakami, Yuko ; 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Individuals with atopic dermatitis are excluded from smallpox vaccination because of their propensity to develop eczema vaccinatum, a disseminated vaccinia virus (VACV) infection. To study the underlying mechanism of the vulnerability of atopic dermatitis patients to VACV infection, we developed a mouse model of eczema vaccinatum. Virus infection of eczematous skin induced severe primary erosive skin lesions, but not in the skin of healthy mice. Eczematous mice exhibited lower natural killer (NK) cell activity but similar cytotoxic T lymphocyte activity and humoral immune responses. The role of NK cells in controlling VACV-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. The proinflammatory cytokine interleukin (IL)-17 reduced NK cell activity in mice with preexisting dermatitis. 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| subjects | Animals Brief Definitive Report Cells, Cultured Dermatitis, Atopic - immunology Dermatitis, Atopic - pathology Disease Models, Animal Disease Susceptibility - immunology Disease Susceptibility - virology Humans Interleukin-17 - genetics Interleukin-17 - immunology Kaposi Varicelliform Eruption - immunology Kaposi Varicelliform Eruption - pathology Kaposi Varicelliform Eruption - virology Killer Cells, Natural - cytology Killer Cells, Natural - immunology Mice Poxvirus Skin - immunology Skin - pathology Skin - virology Smallpox - immunology Vaccinia virus Vaccinia virus - immunology |
| title | Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum |
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