{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:15:23Z","timestamp":1790705723940,"version":"4.1.0"},"reference-count":73,"publisher":"National Academy of Sciences","issue":"27","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1007980"],"award-info":[{"award-number":["APP1007980"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,7,7]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Excessive tumor necrosis factor (TNF) production during some respiratory viral infections is associated with lung pathology and death. We show here that deficiency in TNF also causes significant pathology during respiratory poxvirus infection of mice but has no effect on viral load. TNF deficiency causes increased production of interleukin (IL)-6, IL-10, transforming growth factor beta, and interferon gamma and overactivation of STAT3 signaling. Cytokine blockade, or STAT3 inactivation, ameliorates lung pathology in TNF-deficient mice. The membrane form of TNF alone is necessary and sufficient for regulating inflammation and the prevention of lung pathology. Targeting specific cytokines or cytokine signaling pathways to can ameliorate lung inflammation during respiratory viral infections but the timing and duration of the interventive measures are critical.<\/jats:p>","DOI":"10.1073\/pnas.2004615117","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T20:36:24Z","timestamp":1592858184000},"page":"15935-15946","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":41,"title":["TNF deficiency dysregulates inflammatory cytokine production, leading to lung pathology and death during respiratory poxvirus infection"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8730-1062","authenticated-orcid":false,"given":"Ma. Junaliah","family":"Tuazon Kels","sequence":"first","affiliation":[{"name":"Infection and Immunity Group, Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Ng","sequence":"additional","affiliation":[{"name":"Infection and Immunity Group, Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-7749","authenticated-orcid":false,"given":"Zahrah","family":"Al Rumaih","sequence":"additional","affiliation":[{"name":"Infection and Immunity Group, Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4478-7581","authenticated-orcid":false,"given":"Pratikshya","family":"Pandey","sequence":"additional","affiliation":[{"name":"Viral Immunology and Immunopathology Group, Tasmanian School of Medicine, University of Tasmania, Hobart, TAS 7000, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid R.","family":"Ruuls","sequence":"additional","affiliation":[{"name":"Genmab, 3584 CT Utrecht, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Korner","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P.","family":"Newsome","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3388-2102","authenticated-orcid":false,"given":"Geeta","family":"Chaudhri","sequence":"additional","affiliation":[{"name":"Infection and Immunity Group, Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia;"},{"name":"Research School of Population Health, Australian National University, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6306-4405","authenticated-orcid":false,"given":"Gunasegaran","family":"Karupiah","sequence":"additional","affiliation":[{"name":"Infection and Immunity Group, Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia;"},{"name":"Viral Immunology and Immunopathology Group, Tasmanian School of Medicine, University of Tasmania, Hobart, TAS 7000, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,6,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/39335"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271020"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.15.8093"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1397"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"3504","DOI":"10.4049\/jimmunol.162.6.3504","article-title":"Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin","volume":"162","author":"Bean A. G.","year":"1999","unstructured":"A. G. Bean ., Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin. J.Immunol. 162, 3504\u20133511 (1999).","journal-title":"J.Immunol."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08851.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.169"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4012"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.24.11066"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01310-10"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/330662a0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kes030"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011110"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/385729a0"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/385733a0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1995.0056"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri980"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3786"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020004"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141049"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402949101"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04098-8"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8140422"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2065"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02055-5"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2016.05.001"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-051113-024537"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5344.1803"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1667"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2010.01.005"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00058"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.7.4214-4226.1993"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505180102"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.9.5875-5877.1995"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.12.8301-8309.1996"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02061-06"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.12.6319"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.1.154"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00784"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1266-6"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1539"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02258-X"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.6.3263"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406413200"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737662"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.51.3.296"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.8.4852"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61250-3"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.10.6829"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2012.646986"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2015.1009036"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X10366368"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.09.003"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.07.003"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0603252"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2009.04.008"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.5771"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.07.011"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.07.008"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2009.11.005"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2003.09.004"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.1.257"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.2.187"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1451"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313018200"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-09-0313"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.12.020"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02087"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001455"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep40984"},{"key":"e_1_3_3_71_2","volume-title":"Smallpox and Its Eradication","author":"Fenner F.","year":"1988","unstructured":"F. Fenner, Smallpox and Its Eradication, (World Health Organization, Geneva, 1988), Vol. 6."},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00116-06"},{"key":"e_1_3_3_73_2","doi-asserted-by":"crossref","unstructured":"Z. Al Rumaih . Poxvirus-encoded TNF receptor homolog dampens inflammation and protects the host from uncontrolled lung pathology and death during respiratory infection. bioRxiv:10.1101\/2020.02.24.963520 (25 February 2020).","DOI":"10.1101\/2020.02.24.963520"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2004615117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2004615117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T15:31:53Z","timestamp":1696260713000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2004615117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,22]]},"references-count":73,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2020,7,7]]}},"alternative-id":["10.1073\/pnas.2004615117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2004615117","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2019.12.22.883728","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,22]]},"assertion":[{"value":"2020-06-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}