Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection
Suppressor of cytokine signaling (SOCS) proteins are key regulators of innate and adaptive immunity. There is no described biological role for SOCS4, despite broad expression in the hematopoietic system. We demonstrate that mice lacking functional SOCS4 protein rapidly succumb to infection with a pa...
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| Veröffentlicht in: | PLoS pathogens 2014-05, Vol.10 (5), p.e1004134 |
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| creator | Kedzierski, Lukasz Linossi, Edmond M Kolesnik, Tatiana B Day, E Bridie Bird, Nicola L Kile, Benjamin T Belz, Gabrielle T Metcalf, Donald Nicola, Nicos A Kedzierska, Katherine Nicholson, Sandra E |
| description | Suppressor of cytokine signaling (SOCS) proteins are key regulators of innate and adaptive immunity. There is no described biological role for SOCS4, despite broad expression in the hematopoietic system. We demonstrate that mice lacking functional SOCS4 protein rapidly succumb to infection with a pathogenic H1N1 influenza virus (PR8) and are hypersusceptible to infection with the less virulent H3N2 (X31) strain. In SOCS4-deficient animals, this led to substantially greater weight loss, dysregulated pro-inflammatory cytokine and chemokine production in the lungs and delayed viral clearance. This was associated with impaired trafficking of influenza-specific CD8 T cells to the site of infection and linked to defects in T cell receptor activation. These results demonstrate that SOCS4 is a critical regulator of anti-viral immunity. |
| doi_str_mv | 10.1371/journal.ppat.1004134 |
| format | Article |
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There is no described biological role for SOCS4, despite broad expression in the hematopoietic system. We demonstrate that mice lacking functional SOCS4 protein rapidly succumb to infection with a pathogenic H1N1 influenza virus (PR8) and are hypersusceptible to infection with the less virulent H3N2 (X31) strain. In SOCS4-deficient animals, this led to substantially greater weight loss, dysregulated pro-inflammatory cytokine and chemokine production in the lungs and delayed viral clearance. This was associated with impaired trafficking of influenza-specific CD8 T cells to the site of infection and linked to defects in T cell receptor activation. These results demonstrate that SOCS4 is a critical regulator of anti-viral immunity.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1004134</identifier><identifier>PMID: 24809749</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptive Immunity - genetics ; Animals ; Antiviral agents ; B cells ; Biology and Life Sciences ; Bone marrow ; CD8-Positive T-Lymphocytes - immunology ; Chemokines ; Cytokines ; Cytokines - adverse effects ; Cytokines - metabolism ; Cytoprotection - genetics ; Flow cytometry ; Health aspects ; Immune system ; Infections ; Inflammation - genetics ; Inflammation - metabolism ; Inflammation - prevention & control ; Inflammation Mediators - adverse effects ; Inflammation Mediators - metabolism ; Influenza A Virus, H1N1 Subtype - growth & development ; Influenza A Virus, H1N1 Subtype - immunology ; Kinases ; Lungs ; Lymphocytes ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Transgenic ; Mortality ; Orthomyxoviridae Infections - immunology ; Orthomyxoviridae Infections - virology ; Physiological aspects ; Proteins ; Scholarships & fellowships ; Suppressor of Cytokine Signaling Proteins - physiology ; Swine flu ; T cell receptors ; T cells ; Viral infections ; Viral Load - genetics ; Virulence (Microbiology)</subject><ispartof>PLoS pathogens, 2014-05, Vol.10 (5), p.e1004134</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Kedzierski et al 2014 Kedzierski et al</rights><rights>2014 Kedzierski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Kedzierski L, Linossi EM, Kolesnik TB, Day EB, Bird NL, et al. (2014) Suppressor of Cytokine Signaling 4 (SOCS4) Protects against Severe Cytokine Storm and Enhances Viral Clearance during Influenza Infection. 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There is no described biological role for SOCS4, despite broad expression in the hematopoietic system. We demonstrate that mice lacking functional SOCS4 protein rapidly succumb to infection with a pathogenic H1N1 influenza virus (PR8) and are hypersusceptible to infection with the less virulent H3N2 (X31) strain. In SOCS4-deficient animals, this led to substantially greater weight loss, dysregulated pro-inflammatory cytokine and chemokine production in the lungs and delayed viral clearance. This was associated with impaired trafficking of influenza-specific CD8 T cells to the site of infection and linked to defects in T cell receptor activation. 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Linossi, Edmond M ; Kolesnik, Tatiana B ; Day, E Bridie ; Bird, Nicola L ; Kile, Benjamin T ; Belz, Gabrielle T ; Metcalf, Donald ; Nicola, Nicos A ; Kedzierska, Katherine ; Nicholson, Sandra E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c633t-14962b11256bdb38a4ba89d8e2f0d54860a55c61a6d86f48fc3223dea6fde2e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adaptive Immunity - genetics</topic><topic>Animals</topic><topic>Antiviral agents</topic><topic>B cells</topic><topic>Biology and Life Sciences</topic><topic>Bone marrow</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Chemokines</topic><topic>Cytokines</topic><topic>Cytokines - adverse effects</topic><topic>Cytokines - metabolism</topic><topic>Cytoprotection - genetics</topic><topic>Flow cytometry</topic><topic>Health aspects</topic><topic>Immune system</topic><topic>Infections</topic><topic>Inflammation - genetics</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - prevention & control</topic><topic>Inflammation Mediators - adverse effects</topic><topic>Inflammation Mediators - metabolism</topic><topic>Influenza A Virus, H1N1 Subtype - growth & development</topic><topic>Influenza A Virus, H1N1 Subtype - immunology</topic><topic>Kinases</topic><topic>Lungs</topic><topic>Lymphocytes</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Mortality</topic><topic>Orthomyxoviridae Infections - immunology</topic><topic>Orthomyxoviridae Infections - virology</topic><topic>Physiological aspects</topic><topic>Proteins</topic><topic>Scholarships & fellowships</topic><topic>Suppressor of Cytokine Signaling Proteins - physiology</topic><topic>Swine flu</topic><topic>T cell receptors</topic><topic>T cells</topic><topic>Viral infections</topic><topic>Viral Load - genetics</topic><topic>Virulence (Microbiology)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kedzierski, Lukasz</creatorcontrib><creatorcontrib>Linossi, Edmond M</creatorcontrib><creatorcontrib>Kolesnik, Tatiana B</creatorcontrib><creatorcontrib>Day, E Bridie</creatorcontrib><creatorcontrib>Bird, Nicola L</creatorcontrib><creatorcontrib>Kile, Benjamin T</creatorcontrib><creatorcontrib>Belz, Gabrielle T</creatorcontrib><creatorcontrib>Metcalf, Donald</creatorcontrib><creatorcontrib>Nicola, Nicos A</creatorcontrib><creatorcontrib>Kedzierska, Katherine</creatorcontrib><creatorcontrib>Nicholson, Sandra E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kedzierski, Lukasz</au><au>Linossi, Edmond M</au><au>Kolesnik, Tatiana B</au><au>Day, E Bridie</au><au>Bird, Nicola L</au><au>Kile, Benjamin T</au><au>Belz, Gabrielle T</au><au>Metcalf, Donald</au><au>Nicola, Nicos A</au><au>Kedzierska, Katherine</au><au>Nicholson, Sandra E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>10</volume><issue>5</issue><spage>e1004134</spage><pages>e1004134-</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Suppressor of cytokine signaling (SOCS) proteins are key regulators of innate and adaptive immunity. There is no described biological role for SOCS4, despite broad expression in the hematopoietic system. We demonstrate that mice lacking functional SOCS4 protein rapidly succumb to infection with a pathogenic H1N1 influenza virus (PR8) and are hypersusceptible to infection with the less virulent H3N2 (X31) strain. In SOCS4-deficient animals, this led to substantially greater weight loss, dysregulated pro-inflammatory cytokine and chemokine production in the lungs and delayed viral clearance. This was associated with impaired trafficking of influenza-specific CD8 T cells to the site of infection and linked to defects in T cell receptor activation. These results demonstrate that SOCS4 is a critical regulator of anti-viral immunity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24809749</pmid><doi>10.1371/journal.ppat.1004134</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptive Immunity - genetics Animals Antiviral agents B cells Biology and Life Sciences Bone marrow CD8-Positive T-Lymphocytes - immunology Chemokines Cytokines Cytokines - adverse effects Cytokines - metabolism Cytoprotection - genetics Flow cytometry Health aspects Immune system Infections Inflammation - genetics Inflammation - metabolism Inflammation - prevention & control Inflammation Mediators - adverse effects Inflammation Mediators - metabolism Influenza A Virus, H1N1 Subtype - growth & development Influenza A Virus, H1N1 Subtype - immunology Kinases Lungs Lymphocytes Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Mice, Transgenic Mortality Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - virology Physiological aspects Proteins Scholarships & fellowships Suppressor of Cytokine Signaling Proteins - physiology Swine flu T cell receptors T cells Viral infections Viral Load - genetics Virulence (Microbiology) |
| title | Suppressor of cytokine signaling 4 (SOCS4) protects against severe cytokine storm and enhances viral clearance during influenza infection |
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