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Although this mechanism has been described in coinfection with gram-positive bacteria, it is unclear whether similar mechanisms may impair lung defense against gram-negative infections. Furthermore, precise delineation of the duration of type I IFN-associated susceptibility to bacterial infection remains underexplored. Therefore, we investigated the effects of preceding influenza A virus infection on subsequent challenge with the gram-negative bacteria Escherichia coli or Pseudomonas aeruginosa and the temporal association between IFN expression with susceptibility to Staphylococcus aureus challenge in a mouse model of influenza and bacterial coinfection. Here we demonstrate that preceding influenza A virus led to increased lung E. coli and P. aeruginosa bacterial burden, which was associated with suppression of type 17 immunity and attenuation of antimicrobial peptide expression. Enhanced susceptibility to S. aureus coinfection ceased at day 14 of influenza infection, when influenza-associated type I IFN levels had returned to baseline levels, further suggesting a key role for type I IFN in coinfection pathogenesis. These findings further implicate type I IFN-associated suppression of type 17 immunity and antimicrobial peptide production as a conserved mechanism for enhanced susceptibility to both gram-positive and gram-negative bacterial coinfection during influenza infection.<\/jats:p>","DOI":"10.1152\/ajplung.00338.2014","type":"journal-article","created":{"date-parts":[[2015,5,23]],"date-time":"2015-05-23T02:12:12Z","timestamp":1432347132000},"page":"L158-L167","source":"Crossref","is-referenced-by-count":129,"title":["Influenza-induced type I interferon enhances susceptibility to gram-negative and gram-positive bacterial pneumonia in mice"],"prefix":"10.1152","volume":"309","author":[{"given":"Benjamin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keven M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania;"},{"name":"Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"McHugh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich V.","family":"Scheller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivanarayana","family":"Mandalapu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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