{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:47:08Z","timestamp":1783921628459,"version":"3.55.0"},"reference-count":52,"publisher":"European Respiratory Society (ERS)","issue":"1","funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["Progress"],"award-info":[{"award-number":["Progress"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB-TR84"],"award-info":[{"award-number":["SFB-TR84"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2017,4,7]]},"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>The severity and lethality of influenza A virus (IAV) infections is frequently aggravated by secondary bacterial pneumonia. However, the mechanisms in human lung tissue that provoke this increase in fatality are unknown and therapeutic immune modulatory options are lacking.<\/jats:p><jats:p>We established a human lung<jats:italic>ex vivo<\/jats:italic>co-infection model to investigate innate immune related mechanisms contributing to the susceptibility of secondary pneumococcal pneumonia.<\/jats:p><jats:p>We revealed that type I and III interferon (IFN) inhibits<jats:italic>Streptococcus pneumoniae<\/jats:italic>-induced interleukin (IL)-1\u03b2 release. The lack of IL-1\u03b2 resulted in the repression of bacterially induced granulocyte-macrophage colony-stimulating factor (GM-CSF) liberation. Specific inhibition of IFN receptor I and III-associated tyrosine kinase 2 (Tyk2) completely restored the<jats:italic>S. pneumoniae<\/jats:italic>-induced IL-1\u03b2\u2013GM-CSF axis, leading to a reduction of bacterial growth. A preceding IAV infection of the human alveolus leads to a type I and III IFN-dependent blockade of the early cytokines IL-1\u03b2 and GM-CSF, which are key for orchestrating an adequate innate immune response against bacteria. Their virally induced suppression may result in impaired bacterial clearance and alveolar repair.<\/jats:p><jats:p>Pharmacological inhibition of Tyk2 might be a new treatment option to sustain beneficial endogenous GM-CSF levels in IAV-associated secondary bacterial pneumonia.<\/jats:p>","DOI":"10.1183\/13993003.01953-2016","type":"journal-article","created":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T00:10:19Z","timestamp":1499991019000},"page":"1601953","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Tyk2 as a target for immune regulation in human viral\/bacterial pneumonia"],"prefix":"10.1183","volume":"50","author":[{"given":"Johanna","family":"Berg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Zscheppang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Fatykhova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"T\u00f6nnies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten T.","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Neudecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens C.","family":"R\u00fcckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Eggeling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Schimek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim D.","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Suttorp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hippenstiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas C.","family":"Hocke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2017,7,13]]},"reference":[{"key":"2024101904154602000_50.1.1601953.1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-60-5-759"},{"key":"2024101904154602000_50.1.1601953.2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2008.109785"},{"key":"2024101904154602000_50.1.1601953.3","doi-asserted-by":"publisher","DOI":"10.1007\/82_2014_394"},{"key":"2024101904154602000_50.1.1601953.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.02.002"},{"key":"2024101904154602000_50.1.1601953.5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35412"},{"key":"2024101904154602000_50.1.1601953.6","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01269-12"},{"key":"2024101904154602000_50.1.1601953.7","doi-asserted-by":"publisher","DOI":"10.1038\/nm1765"},{"key":"2024101904154602000_50.1.1601953.8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1300324"},{"key":"2024101904154602000_50.1.1601953.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.02.006"},{"key":"2024101904154602000_50.1.1601953.10","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.93"},{"key":"2024101904154602000_50.1.1601953.11","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxn071"},{"key":"2024101904154602000_50.1.1601953.12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301237"},{"key":"2024101904154602000_50.1.1601953.13","doi-asserted-by":"crossref","first-page":"4142","DOI":"10.1182\/blood.V84.12.4142.bloodjournal84124142","article-title":"Regulation of cytokine expression by interferon-\u03b1 in human bone marrow stromal cells: inhibition of hematopoietic growth factors and induction of interleukin-1 receptor antagonist","volume":"84","author":"Aman","year":"1994","journal-title":"Blood"},{"key":"2024101904154602000_50.1.1601953.14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1365-2141.1995.tb05237.x","article-title":"Interferon-\u03b1 (IFN-\u03b1) inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF) expression at the post-transcriptional level in murine bone marrow stromal cells","volume":"91","author":"G\u00f6llner","year":"1995","journal-title":"Br J Haematol"},{"key":"2024101904154602000_50.1.1601953.15","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201012-2036OC"},{"key":"2024101904154602000_50.1.1601953.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.04.001"},{"key":"2024101904154602000_50.1.1601953.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2011.08.022"},{"key":"2024101904154602000_50.1.1601953.18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62139"},{"key":"2024101904154602000_50.1.1601953.19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5212"},{"key":"2024101904154602000_50.1.1601953.20","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00415.2010"},{"key":"2024101904154602000_50.1.1601953.21","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101413"},{"key":"2024101904154602000_50.1.1601953.22","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201311-2041LE"},{"key":"2024101904154602000_50.1.1601953.23","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31822d7bf0"},{"key":"2024101904154602000_50.1.1601953.24","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201305-0954LE"},{"key":"2024101904154602000_50.1.1601953.25","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018887501927"},{"key":"2024101904154602000_50.1.1601953.26","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis455"},{"key":"2024101904154602000_50.1.1601953.27","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00186911"},{"key":"2024101904154602000_50.1.1601953.28","first-page":"82","article-title":"Induction of pro- and anti-inflammatory molecules in a mouse model of pneumococcal pneumonia after influenza","volume":"57","author":"Smith","year":"2007","journal-title":"Comp Med"},{"key":"2024101904154602000_50.1.1601953.29","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200812-1837OC"},{"key":"2024101904154602000_50.1.1601953.30","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00338.2014"},{"key":"2024101904154602000_50.1.1601953.31","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(00)00171-1"},{"key":"2024101904154602000_50.1.1601953.32","doi-asserted-by":"publisher","DOI":"10.1038\/nri1604"},{"key":"2024101904154602000_50.1.1601953.33","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01703-09"},{"key":"2024101904154602000_50.1.1601953.34","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.virol.2015.03.048","article-title":"RIG-I and TLR3 are both required for maximum interferon induction by influenza virus in human lung alveolar epithelial cells","volume":"482","author":"Wu","year":"2015","journal-title":"Virology"},{"key":"2024101904154602000_50.1.1601953.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033732"},{"key":"2024101904154602000_50.1.1601953.36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049856"},{"key":"2024101904154602000_50.1.1601953.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2015.02.003"},{"key":"2024101904154602000_50.1.1601953.38","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199903)187:4<475::AID-PATH268>3.0.CO;2-N"},{"key":"2024101904154602000_50.1.1601953.39","doi-asserted-by":"crossref","first-page":"932","DOI":"10.4049\/jimmunol.149.3.932","article-title":"A kinetic study of immune mediators in the lungs of mice infected with influenza A virus","volume":"149","author":"Hennet","year":"1992","journal-title":"J Immunol"},{"key":"2024101904154602000_50.1.1601953.40","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260611"},{"key":"2024101904154602000_50.1.1601953.41","doi-asserted-by":"publisher","DOI":"10.1089\/10799900152434358"},{"key":"2024101904154602000_50.1.1601953.42","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00022.2012"},{"key":"2024101904154602000_50.1.1601953.43","doi-asserted-by":"crossref","first-page":"e0124593","DOI":"10.1371\/journal.pone.0124593","article-title":"Delivery of GM-CSF to protect against influenza pneumonia","volume":"10","author":"Subramaniam","year":"2015","journal-title":"PLoS One"},{"key":"2024101904154602000_50.1.1601953.44","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00303.2010"},{"key":"2024101904154602000_50.1.1601953.45","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.2001.1789"},{"key":"2024101904154602000_50.1.1601953.46","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606413"},{"key":"2024101904154602000_50.1.1601953.47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904000"},{"key":"2024101904154602000_50.1.1601953.48","doi-asserted-by":"publisher","DOI":"10.4155\/ppa.14.23"},{"key":"2024101904154602000_50.1.1601953.49","first-page":"55","article-title":"Influenza infection and COPD","volume":"2","author":"Mallia","year":"2007","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"2024101904154602000_50.1.1601953.50","first-page":"1","article-title":"Influenza and pneumococcal vaccinations for patients with chronic obstructive pulmonary disease (COPD): an evidence-based review","volume":"12","author":"Sehatzadeh","year":"2012","journal-title":"Ont Health Technol Assess Ser"},{"key":"2024101904154602000_50.1.1601953.51","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2013-204282"},{"key":"2024101904154602000_50.1.1601953.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2012.04.008"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.01953-2016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T06:42:24Z","timestamp":1740379344000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.01953-2016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,7,13]]},"published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1183\/13993003.01953-2016"],"URL":"https:\/\/doi.org\/10.1183\/13993003.01953-2016","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7]]}}}