title: Tumor necrosis factor-related apoptosis-inducing ligand translates neonatal respiratory infection into chronic lung disease.
abstract: Respiratory infections in early life can lead to chronic respiratory disease. Chlamydia infections are common causes of respiratory disease, particularly pneumonia in neonates, and are linked to permanent reductions in pulmonary function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. Here we identify novel roles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in promoting Chlamydia respiratory infection-induced pathology in early life, and subsequent chronic lung disease. By infecting TRAIL-deficient neonatal mice and using neutralizing antibodies against this factor and its receptors in wild-type mice, we demonstrate that TRAIL is critical in promoting infection-induced histopathology, inflammation, and mucus hypersecretion, as well as subsequent alveolar enlargement and impaired lung function. This suggests that therapeutic agents that target TRAIL or its receptors may be effective treatments for early-life respiratory infections and associated chronic lung disease.
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: M R
authors.initials: MR
authors.lastname: Starkey
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: D H
authors.initials: DH
authors.lastname: Nguyen
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: A T
authors.initials: AT
authors.lastname: Essilfie
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: R Y
authors.initials: RY
authors.lastname: Kim
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: L M
authors.initials: LM
authors.lastname: Hatchwell
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Collison
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: P S
authors.initials: PS
authors.lastname: Foster
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: J C
authors.initials: JC
authors.lastname: Horvat
authors.affiliation: 1] Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia [2] Pediatric Respiratory and Sleep Medicine Unit, Newcastle Children's Hospital, Kaleidoscope, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Mattes
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, New Lambton Heights, Newcastle, New South Wales, Australia.
authors.forename: P M
authors.initials: PM
authors.lastname: Hansbro
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D002690:Chlamydia Infections / Q000378:metabolism; D023502:Chlamydia muridarum; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand
references.citation: J Asthma. 2009 Nov;46(9):967-8
references.pmid: 19905928
references.citation: Am J Respir Crit Care Med. 2007 Sep 15;176(6):556-64
references.pmid: 17600276
references.citation: Science. 1997 Aug 8;277(5327):815-8
references.pmid: 9242610
references.citation: Respir Res. 2006 Aug 07;7:107
references.pmid: 16893457
references.citation: Thorax. 2012 Jul;67(7):588-99
references.pmid: 22387445
references.citation: Blood. 2009 Oct 29;114(18):3854-63
references.pmid: 19690337
references.citation: J Immunol. 2008 Oct 1;181(7):4918-25
references.pmid: 18802095
references.citation: PLoS Pathog. 2011 May;7(5):e1001339
references.pmid: 21573182
references.citation: J Immunol. 2012 May 1;188(9):4611-20
references.pmid: 22461699
references.citation: J Pediatr. 1986 May;108(5 Pt 1):659-64
references.pmid: 3701509
references.citation: Am J Respir Crit Care Med. 2008 May 1;177(9):959-69
references.pmid: 18263801
references.citation: Immunity. 1995 Dec;3(6):673-82
references.pmid: 8777713
references.citation: Mod Pathol. 2003 Jan;16(1):1-7
references.pmid: 12527706
references.citation: Cancer Res. 2004 Feb 1;64(3):1037-43
references.pmid: 14871835
references.citation: Pediatr Radiol. 1995;25(8):646-8
references.pmid: 8570321
references.citation: J Immunol. 2008 Sep 1;181(5):3486-94
references.pmid: 18714021
references.citation: Pediatr Infect Dis. 1982 Jan-Feb;1(1):29-33
references.pmid: 7177892
references.citation: Nat Med. 2013 Feb;19(2):232-7
references.pmid: 23334847
references.citation: Pharmacol Ther. 2008 Mar;117(3):313-53
references.pmid: 18234348
references.citation: PLoS One. 2012;7(8):e42588
references.pmid: 22870337
references.citation: J Virol. 2005 Jun;79(12):7658-63
references.pmid: 15919918
references.citation: Immunity. 1997 Dec;7(6):831-6
references.pmid: 9430228
references.citation: J Immunol. 2008 Feb 15;180(4):2225-32
references.pmid: 18250429
references.citation: Science. 1997 Aug 8;277(5327):818-21
references.pmid: 9242611
references.citation: J Allergy Clin Immunol. 2010 Mar;125(3):617-25, 625.e1-625.e6
references.pmid: 20122715
references.citation: J Exp Med. 2004 Feb 16;199(4):437-48
references.pmid: 14769851
references.citation: J Exp Med. 2012 Oct 22;209(11):1937-52
references.pmid: 23071253
references.citation: J Virol. 2003 Sep;77(17):9156-72
references.pmid: 12915532
references.citation: Science. 1997 Apr 4;276(5309):111-3
references.pmid: 9082980
references.citation: PLoS One. 2012;7(6):e39460
references.pmid: 22724018
references.citation: Nat Med. 2007 Nov;13(11):1308-15
references.pmid: 17934471
references.citation: J Exp Med. 1999 May 3;189(9):1451-60
references.pmid: 10224285
references.citation: Eur Respir J. 2009 Feb;33(2):360-7
references.pmid: 19010996
references.citation: Immunol Cell Biol. 2005 Oct;83(5):511-9
references.pmid: 16174101
references.citation: Mucosal Immunol. 2013 May;6(3):569-79
references.pmid: 23131786
references.citation: J Immunol. 2010 Apr 15;184(8):4159-69
references.pmid: 20228193
references.citation: J Immunol. 2008 Aug 1;181(3):2092-102
references.pmid: 18641348
references.citation: Immunity. 1997 Dec;7(6):813-20
references.pmid: 9430226
references.citation: Vaccine. 2007 Nov 23;25(48):8154-62
references.pmid: 17950502
references.citation: Pharmacol Ther. 2004 Mar;101(3):193-210
references.pmid: 15030999
references.citation: JAMA. 1986 Jun 27;255(24):3374-7
references.pmid: 3712696
references.citation: J Exp Med. 2008 Dec 22;205(13):3065-77
references.pmid: 19064696
references.citation: Clin Exp Pharmacol Physiol. 2009 Nov;36(11):1049-53
references.pmid: 19656161
references.citation: PLoS Pathog. 2011 Oct;7(10):e1002244
references.pmid: 21998577
references.citation: Am J Respir Cell Mol Biol. 2010 Jun;42(6):697-705
references.pmid: 19635930
references.citation: Crit Rev Immunol. 2009;29(4):275-305
references.pmid: 19673684
references.citation: Science. 2013 Mar 1;339(6123):1088-92
references.pmid: 23449591
references.citation: Eur Respir J. 2011 Jan;37(1):53-64
references.pmid: 20525707
references.citation: Am J Respir Crit Care Med. 2005 May 15;171(10):1083-8
references.pmid: 15735056
references.citation: Eur Radiol. 2001;11(12):2581-4
references.pmid: 11734962
references.citation: Lab Invest. 2011 Oct;91(10):1530-9
references.pmid: 21769086
references.citation: Thorax. 2010 Dec;65(12):1053-60
references.pmid: 20965927