{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:31:19Z","timestamp":1792675879672,"version":"4.5.0"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T00:00:00Z","timestamp":1462233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI04905"],"award-info":[{"award-number":["R01AI04905"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM110732"],"award-info":[{"award-number":["P30GM110732"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005834","name":"Francis Family Foundation","doi-asserted-by":"publisher","award":["PBF"],"award-info":[{"award-number":["PBF"]}],"id":[{"id":"10.13039\/100005834","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,7,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bacterial superinfections are a primary cause of death during influenza pandemics and epidemics. Type I interferon (IFN) signaling contributes to increased susceptibility of mice to bacterial superinfection around day 7 post-influenza A virus (IAV) infection. Here we demonstrate that the reduced susceptibility to methicillin-resistant\n                    <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n                    (MRSA) at day 3 post-IAV infection, which we previously reported was due to interleukin-13 (IL-13)\/IFN-\u03b3 responses, is also dependent on type I IFN signaling and its subsequent requirement for protective IL-13 production. We found, through utilization of blocking antibodies, that reduced susceptibility to MRSA at day 3 post-IAV infection was IFN-\u03b2 dependent, whereas the increased susceptibility at day 7 was IFN-\u03b1 dependent. IFN-\u03b2 signaling early in IAV infection was required for MRSA clearance, whereas IFN-\u03b1 signaling late in infection was not, though it did mediate increased susceptibility to MRSA at that time. Type I IFN receptor (IFNAR) signaling in CD11c\n                    <jats:sup>+<\/jats:sup>\n                    and Ly6G\n                    <jats:sup>+<\/jats:sup>\n                    cells was required for the observed reduced susceptibility at day 3 post-IAV infection. Depletion of Ly6G\n                    <jats:sup>+<\/jats:sup>\n                    cells in mice in which IFNAR signaling was either blocked or deleted indicated that Ly6G\n                    <jats:sup>+<\/jats:sup>\n                    cells were responsible for the IFNAR signaling-dependent susceptibility to MRSA superinfection at day 7 post-IAV infection. Thus, during IAV infection, the temporal differences in type I IFN signaling increased bactericidal activity of both CD11c\n                    <jats:sup>+<\/jats:sup>\n                    and Ly6G\n                    <jats:sup>+<\/jats:sup>\n                    cells at day 3 and reduced effector function of Ly6G\n                    <jats:sup>+<\/jats:sup>\n                    cells at day 7. The temporal differential outcomes induced by IFN-\u03b2 (day 3) and IFN-\u03b1 (day 7) signaling through the same IFNAR resulted in differential susceptibility to MRSA at 3 and 7\u00a0days post-IAV infection.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Approximately 114,000 hospitalizations and 40,000 annual deaths in the United States are associated with influenza A virus (IAV) infections. Frequently, these deaths are due to community-acquired Gram-positive bacterial species, many of which show increasing resistance to antibiotic therapy. Severe complications, including parapneumonic empyema and necrotizing pneumonia, can arise, depending on virulence factors expressed by either the virus or bacteria. Unfortunately, we are unable to control the expression of these virulence factors, making host responses a logical target for therapeutic interventions. Moreover, interactions between virus, host, and bacteria that exacerbate IAV-related morbidities and mortalities are largely unknown. Here, we show that type I interferon (IFN) expression can modulate susceptibility to methicillin-resistant\n                    <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n                    (MRSA) infection, with IFN-\u03b2 reducing host susceptibility to MRSA infection while IFN-\u03b1 increases susceptibility. Our data indicate that treatments designed to augment IFN-\u03b2 and\/or inhibit IFN-\u03b1 production around day 7 post-IAV infection could reduce susceptibility to deadly superinfections.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00506-16","type":"journal-article","created":{"date-parts":[[2016,5,3]],"date-time":"2016-05-03T22:08:15Z","timestamp":1462313295000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":56,"title":["Differential Type I Interferon Signaling Is a Master Regulator of Susceptibility to Postinfluenza Bacterial Superinfection"],"prefix":"10.1128","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-2594","authenticated-orcid":false,"given":"Kelly M.","family":"Shepardson","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachelle V.","family":"Morton","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin R.","family":"Prigge","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward E.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor C.","family":"Huber","sequence":"additional","affiliation":[{"name":"Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Rynda-Apple","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Montana State University, Bozeman, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2012.01.003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3231"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.194139"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/650204"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiq113"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(06)70466-2"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35412"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444582"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1765"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1684"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.08.014"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101664"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1863"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00727.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2005.24.614"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni978"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.8.4279"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050821"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-428672"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091158"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01718-06"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02144-08"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.05.007"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.120"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003951"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35879"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201055"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041879"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002194"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01269-12"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00338.2014"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140825"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0086MA"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.8.4465"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040769"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.01.002"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.07.019"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.11.053"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.6.3907"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2011.10.009"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303049"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R700006200"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1141"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.2.871"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.09.003"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.03.018"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/35073080"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612023393288"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.02.002"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004998"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235214"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1235208"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2667"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1086\/498915"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit527"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301237"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00143.x"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.09.022"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08476"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501553"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90644-6"},{"key":"e_1_3_2_63_2","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council","year":"2011","unstructured":"National Research Council. 2011. Guide for the care and use of laboratory animals, 8th ed. National Academies Press, Washington, DC."},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2013.0015"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2014.09.004"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63950-8"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2006.26.804"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01000-07"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00506-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.00506-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T21:00:41Z","timestamp":1646686841000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.00506-16"}},"subtitle":[],"editor":[{"given":"Christine A.","family":"Biron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,7,6]]},"references-count":67,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,7,6]]}},"alternative-id":["10.1128\/mBio.00506-16"],"URL":"https:\/\/doi.org\/10.1128\/mbio.00506-16","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,6]]},"assertion":[{"value":"2016-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-03-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00506-16"}}