Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection.
Epithelial transport of ions and water
Influenza
Innate immunity
Pulmonology
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
02 Oct 2023
02 Oct 2023
Historique:
received:
08
07
2022
accepted:
10
08
2023
pubmed:
15
8
2023
medline:
15
8
2023
entrez:
15
8
2023
Statut:
epublish
Résumé
Secondary lung infection by inhaled Staphylococcus aureus (SA) is a common and lethal event for individuals infected with influenza A virus (IAV). How IAV disrupts host defense to promote SA infection in lung alveoli, where fatal lung injury occurs, is not known. We addressed this issue using real-time determinations of alveolar responses to IAV in live, intact, perfused lungs. Our findings show that IAV infection blocked defensive alveolar wall liquid (AWL) secretion and induced airspace liquid absorption, thereby reversing normal alveolar liquid dynamics and inhibiting alveolar clearance of inhaled SA. Loss of AWL secretion resulted from inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in the alveolar epithelium, and airspace liquid absorption was caused by stimulation of the alveolar epithelial Na+ channel (ENaC). Loss of AWL secretion promoted alveolar stabilization of inhaled SA, but rescue of AWL secretion protected against alveolar SA stabilization and fatal SA-induced lung injury in IAV-infected mice. These findings reveal a central role for AWL secretion in alveolar defense against inhaled SA and identify AWL inhibition as a critical mechanism of IAV lung pathogenesis. AWL rescue may represent a new therapeutic approach for IAV-SA coinfection.
Identifiants
pubmed: 37581936
pii: 163402
doi: 10.1172/JCI163402
pmc: PMC10541650
doi:
pii:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007647
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI151229
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL036024
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL164821
Pays : United States
Organisme : NHLBI NIH HHS
ID : R03 HL154276
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001873
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL125514
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL122730
Pays : United States
Références
Am J Respir Cell Mol Biol. 2013 Aug;49(2):180-9
pubmed: 23492192
J Clin Invest. 2016 Apr 1;126(4):1566-80
pubmed: 26999599
Am J Physiol Lung Cell Mol Physiol. 2015 Oct 1;309(7):L687-99
pubmed: 26209275
J Biol Chem. 2010 Nov 5;285(45):34939-49
pubmed: 20801871
Am J Respir Cell Mol Biol. 2015 Oct;53(4):459-70
pubmed: 25693001
J Infect Chemother. 2019 Feb;25(2):129-136
pubmed: 30448361
Lancet. 2018 Nov 10;392(10159):1736-1788
pubmed: 30496103
N Engl J Med. 2015 Jul 30;373(5):415-27
pubmed: 26172429
Am J Physiol Lung Cell Mol Physiol. 2012 Jul;303(2):L152-60
pubmed: 22637155
Sci Rep. 2019 Sep 17;9(1):13460
pubmed: 31530897
Methods Mol Biol. 2011;741:471-88
pubmed: 21594802
Am J Respir Cell Mol Biol. 2007 Jun;36(6):688-96
pubmed: 17290033
Hum Pathol. 2008 Mar;39(3):368-76
pubmed: 18045644
J Biol Chem. 1999 Feb 5;274(6):3602-9
pubmed: 9920908
Eur Respir J. 2009 Nov;34(5):1148-58
pubmed: 19541719
N Engl J Med. 2015 Feb 26;372(9):835-45
pubmed: 25714161
Am J Physiol Lung Cell Mol Physiol. 2006 Apr;290(4):L649-L660
pubmed: 16258001
Am Rev Respir Dis. 1981 May;123(5):533-41
pubmed: 7015935
Am J Respir Cell Mol Biol. 2010 Apr;42(4):450-60
pubmed: 19520922
J Cyst Fibros. 2016 Jan;15(1):67-73
pubmed: 25769931
J Immunol. 2006 Jan 1;176(1):416-25
pubmed: 16365435
Am J Physiol Lung Cell Mol Physiol. 2006 Feb;290(2):L242-9
pubmed: 16143588
Am Rev Respir Dis. 1986 Nov;134(5):1040-4
pubmed: 3777666
Am Rev Respir Dis. 1984 Aug;130(2):225-30
pubmed: 6547813
Semin Respir Crit Care Med. 2019 Feb;40(1):31-39
pubmed: 31060086
Antimicrob Agents Chemother. 2021 Oct 18;65(11):e0134121
pubmed: 34491806
J Appl Physiol (1985). 2003 Jan;94(1):343-52
pubmed: 12391048
Semin Immunopathol. 2012 Mar;34(2):281-97
pubmed: 22037948
Front Cell Infect Microbiol. 2020 Mar 17;10:107
pubmed: 32257966
Viruses. 2019 Jan 29;11(2):
pubmed: 30699912
Biochim Biophys Acta. 2009 Jun;1788(6):1341-9
pubmed: 19328185
Am J Physiol Lung Cell Mol Physiol. 2004 Aug;287(2):L366-73
pubmed: 15121635
N Engl J Med. 2005 Dec 15;353(24):2559-67
pubmed: 16354892
Nat Genet. 1996 Mar;12(3):325-8
pubmed: 8589728
Sci Rep. 2021 Jul 22;11(1):15048
pubmed: 34294832
Am J Physiol Lung Cell Mol Physiol. 2014 Jan 1;306(1):L50-7
pubmed: 24213916
Kidney Int. 2001 Aug;60(2):455-61
pubmed: 11473626
JCI Insight. 2018 Oct 18;3(20):
pubmed: 30333319
Annu Rev Physiol. 2013;75:593-615
pubmed: 23398155
J Cyst Fibros. 2014 Sep;13(5):515-9
pubmed: 24618508
Am J Physiol Lung Cell Mol Physiol. 2002 Apr;282(4):L599-608
pubmed: 11880284
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1937-42
pubmed: 12578973
Am J Respir Cell Mol Biol. 1994 Jun;10(6):613-24
pubmed: 8003339
Pediatrics. 2008 Oct;122(4):805-11
pubmed: 18829805
J Exp Med. 2016 Aug 22;213(9):1851-64
pubmed: 27526712
Infect Control Hosp Epidemiol. 2022 Feb;43(2):212-217
pubmed: 33890558
J Clin Invest. 2018 Mar 1;128(3):1074-1086
pubmed: 29431734
Am J Physiol Lung Cell Mol Physiol. 2013 May 1;304(9):L582-92
pubmed: 23457187
Am J Physiol Lung Cell Mol Physiol. 2001 Dec;281(6):L1327-34
pubmed: 11704526
Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):E2308-16
pubmed: 23645634
FASEB J. 2015 Jul;29(7):2712-25
pubmed: 25795456
Clin Infect Dis. 2019 Jan 18;68(3):365-372
pubmed: 29893805
PLoS Pathog. 2015 Mar 12;11(3):e1004661
pubmed: 25764299
JCI Insight. 2021 Mar 22;6(6):
pubmed: 33749665
Am J Physiol Lung Cell Mol Physiol. 2020 Nov 1;319(5):L770-L785
pubmed: 32877225
J Clin Invest. 1994 Feb;93(2):737-49
pubmed: 7509347
J Infect Dis. 2010 Feb 15;201(4):508-15
pubmed: 20078212
J Biol Chem. 1992 Jun 25;267(18):12742-52
pubmed: 1377674
Respir Physiol Neurobiol. 2007 Dec 15;159(3):283-300
pubmed: 17689299
Am J Physiol Lung Cell Mol Physiol. 2004 Aug;287(2):L382-92
pubmed: 15107294
JCI Insight. 2019 Feb 7;4(3):
pubmed: 30728333
Am J Physiol Lung Cell Mol Physiol. 2004 Feb;286(2):L231-46
pubmed: 14711798
Infect Drug Resist. 2017 Apr 20;10:121-134
pubmed: 28458567
J Clin Invest. 1974 Sep;54(3):519-28
pubmed: 4853956
Crit Care Med. 2012 May;40(5):1487-98
pubmed: 22511131
J Cell Sci. 2008 Sep 1;121(Pt 17):2814-23
pubmed: 18682497
Angew Chem Int Ed Engl. 2021 Apr 19;60(17):9467-9473
pubmed: 33464672
JAMA. 2013 Jan 16;309(3):275-82
pubmed: 23321766
J Appl Physiol. 1975 Nov;39(5):773-9
pubmed: 1102518
PLoS Pathog. 2019 Jan 25;15(1):e1007560
pubmed: 30682165
J Immunol. 2014 Apr 1;192(7):3301-7
pubmed: 24563256
Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4964-9
pubmed: 16549766
J Clin Pharm Ther. 2021 Apr;46(2):286-294
pubmed: 33285018
Sci Rep. 2015 Oct 14;5:15159
pubmed: 26464114
Am J Physiol Lung Cell Mol Physiol. 2013 Mar 15;304(6):L428-37
pubmed: 23292809
Immunity. 2017 Dec 19;47(6):1169-1181.e7
pubmed: 29246444
BMC Infect Dis. 2021 Sep 21;21(1):985
pubmed: 34548027
Am J Physiol Lung Cell Mol Physiol. 2006 Oct;291(4):L610-8
pubmed: 16679376
Am J Physiol Lung Cell Mol Physiol. 2009 Jun;296(6):L901-10
pubmed: 19304909
J Infect Dis. 2011 Mar 15;203(6):880-8
pubmed: 21278211
J Infect Dis. 2008 Oct 1;198(7):962-70
pubmed: 18710327
Biomolecules. 2022 Sep 10;12(9):
pubmed: 36139112