{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T05:15:58Z","timestamp":1793078158765,"version":"4.5.0"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The clinical response to influenza infection ranges from mild disease to severe pneumonia and it remains unclear whether the inflammatory response to infection is protective or pathogenic. We have defined a novel role for neutrophils in ameliorating lung injury during influenza infection, thereby limiting development of severe disease. Infection of neutrophil-depleted mice with influenza virus HKx31 (H3N2) led to rapid weight loss, pneumonia, and death. Neutropenia was associated with enhanced virus replication in the respiratory tract; however, viral titers were declining at the time of death, leading us to investigate other factors contributing to mortality. In addition to thymic atrophy, lymphopenia, and viremic spread, depletion of neutrophils led to exacerbated pulmonary inflammation, edema, and respiratory dysfunction. Thus, while it is well established that neutrophils contribute to lung injury in a range of pathological conditions, reduced numbers or impaired neutrophil function can facilitate progression of mild influenza to severe clinical disease.<\/jats:p>","DOI":"10.4049\/jimmunol.0902497","type":"journal-article","created":{"date-parts":[[2009,11,16]],"date-time":"2009-11-16T21:55:14Z","timestamp":1258408514000},"page":"7441-7450","source":"Crossref","is-referenced-by-count":277,"title":["Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection"],"prefix":"10.1093","volume":"183","author":[{"given":"Michelle D","family":"Tate","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Mo","family":"Deng","sequence":"additional","affiliation":[{"name":"World Health Organisation Collaborating Centre for Reference and Research on Influenza , North Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica E","family":"Jones","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine, University of Melbourne , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary P","family":"Anderson","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Medicine, University of Melbourne , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G","family":"Brooks","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C","family":"Reading","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne , Melbourne, Victoria,","place":["Australia"]},{"name":"World Health Organisation Collaborating Centre for Reference and Research on Influenza , North Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,1]]},"reference":[{"key":"2026012811270562200_R1","first-page":"303","article-title":"Pathogenicity of influenza virus.","volume-title":"Microbiol. 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Res.","year":"2008"},{"key":"2026012811270562200_R9","first-page":"2772","article-title":"Neutrophils play an essential role in cooperation with antibody in both protection against and recovery from pulmonary infection with influenza virus in mice.","volume-title":"J. Virol.","year":"2008"},{"key":"2026012811270562200_R10","first-page":"2399","article-title":"Selective expression of Ly-6G on myeloid lineage cells in mouse bone marrow: RB6-8C5 mAb to granulocyte-differentiation antigen (Gr-1) detects members of the Ly-6 family.","volume-title":"J. Immunol.","year":"1993"},{"key":"2026012811270562200_R11","first-page":"98","article-title":"Successful elimination of memory-type CD8+ T cell subsets by the administration of anti-Gr-1 monoclonal antibody in vivo.","volume-title":"Cell. Immunol.","year":"2003"},{"key":"2026012811270562200_R12","first-page":"898","article-title":"Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea.","volume-title":"J. Virol.","year":"1996"},{"key":"2026012811270562200_R13","first-page":"1836","article-title":"Administration of anti-granulocyte mAb RB6-8C5 impairs the resistance of mice to Listeria monocytogenes infection.","volume-title":"J. Immunol.","year":"1994"},{"key":"2026012811270562200_R14","first-page":"64","article-title":"Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice.","volume-title":"J. Leukocyte Biol.","year":"2008"},{"key":"2026012811270562200_R15","first-page":"615","article-title":"Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin.","volume-title":"J. Gen. Virol.","year":"1994"},{"key":"2026012811270562200_R16","first-page":"2978","article-title":"CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen.","volume-title":"J. Immunol.","year":"2000"},{"key":"2026012811270562200_R17","first-page":"205","article-title":"CD11b regulates recruitment of alveolar macrophages but not pulmonary dendritic cells after pneumococcal challenge.","volume-title":"J. Infect. Dis.","year":"2006"},{"key":"2026012811270562200_R18","first-page":"1882","article-title":"Diverse and potent chemokine production by lung CD11bhigh dendritic cells in homeostasis and in allergic lung inflammation.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012811270562200_R19","first-page":"1153","article-title":"Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus.","volume-title":"J. Exp. Med.","year":"2006"},{"key":"2026012811270562200_R20","first-page":"6284","article-title":"Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides.","volume-title":"J. Immunol.","year":"1999"},{"key":"2026012811270562200_R21","first-page":"762","article-title":"Fas\/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice.","volume-title":"Am. J. Respir. Crit. Care Med.","year":"2001"},{"key":"2026012811270562200_R22","first-page":"1233","article-title":"Kinetic analysis of Ly-6 gene induction in a T lymphoma by interferons and interleukin 1, and demonstration of Ly-6 inducibility in diverse cell types.","volume-title":"Eur. J. Immunol.","year":"1989"},{"key":"2026012811270562200_R23","first-page":"621","article-title":"Type I interferon is the primary regulator of inducible Ly-6C expression on T cells.","volume-title":"J. 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Med.","year":"1986"},{"key":"2026012811270562200_R45","first-page":"644","article-title":"Deactivation of alveolar macrophages in septic neutropenic ARDS.","volume-title":"Chest","year":"2003"},{"key":"2026012811270562200_R46","first-page":"S195","article-title":"Neutrophils and acute lung injury.","volume-title":"Crit. Care Med.","year":"2003"},{"key":"2026012811270562200_R47","first-page":"921","article-title":"Oxygen-induced lung microvascular injury in neutropenic rabbits and lambs.","volume-title":"J. Appl. Physiol.","year":"1985"},{"key":"2026012811270562200_R48","first-page":"1126","article-title":"Effects of hyperoxia on alveolar permeability of neutropenic rabbits.","volume-title":"J. Appl. Physiol.","year":"1986"},{"key":"2026012811270562200_R49","first-page":"1277","article-title":"Oxidant injury of lung parenchymal cells.","volume-title":"J. Clin. 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Med.","year":"2000"},{"key":"2026012811270562200_R67","first-page":"142","article-title":"Neutrophil interaction with influenza-infected epithelial cells.","volume-title":"Blood","year":"1988"},{"key":"2026012811270562200_R68","first-page":"2448","article-title":"Evidence for phagocytosis of influenza virus-infected, apoptotic cells by neutrophils and macrophages in mice.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012811270562200_R69","first-page":"3952","article-title":"Neutrophil deactivation by influenza A virus: role of hemagglutinin binding to specific sialic acid-bearing cellular proteins.","volume-title":"J. 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