Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study.
Adolescent
Birth Cohort
Cohort Studies
Female
Humans
Imidazoles
/ immunology
Immunity, Innate
Interferons
/ immunology
Leukocytes, Mononuclear
/ immunology
Male
Oligodeoxyribonucleotides
/ immunology
Picornaviridae Infections
/ immunology
Respiratory Syncytial Virus Infections
/ immunology
Respiratory Syncytial Virus, Human
/ immunology
Respiratory Tract Infections
/ immunology
Rhinovirus
/ immunology
SARS-CoV-2
Sex Factors
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 12 2021
09 12 2021
Historique:
received:
02
07
2021
accepted:
23
11
2021
entrez:
10
12
2021
pubmed:
11
12
2021
medline:
21
12
2021
Statut:
epublish
Résumé
The mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34-2.06-fold lower in males than females (P = 0.018 - < 0.001). IFN-β, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.
Identifiants
pubmed: 34887467
doi: 10.1038/s41598-021-03044-x
pii: 10.1038/s41598-021-03044-x
pmc: PMC8660814
doi:
Substances chimiques
Imidazoles
0
Oligodeoxyribonucleotides
0
Interferons
9008-11-1
resiquimod
V3DMU7PVXF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23741Subventions
Organisme : Medical Research Council
ID : MR/K002449/1
Pays : United Kingdom
Organisme : European Research Council
Pays : International
Organisme : Medical Research Council
ID : G0601361
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K002449/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S025340/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L012693/1
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
Références
N Engl J Med. 2021 Feb 11;384(6):497-511
pubmed: 33264556
Am J Physiol Lung Cell Mol Physiol. 2019 Dec 1;317(6):L893-L903
pubmed: 31513433
BMJ. 2017 Dec 11;359:j5560
pubmed: 29229663
Immunity. 2017 May 16;46(5):875-890.e6
pubmed: 28514692
J Immunol Methods. 2008 Dec 31;339(2):132-40
pubmed: 18848564
BMJ. 2011 May 11;342:d2863
pubmed: 21562005
Allergy. 2009 Mar;64(3):375-86
pubmed: 19175599
Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13562-7
pubmed: 18768794
Thorax. 2002 Apr;57(4):328-32
pubmed: 11923551
Nature. 2011 Apr 28;472(7344):481-5
pubmed: 21478870
Antiviral Res. 2020 Jul;179:104811
pubmed: 32360182
Pediatr Allergy Immunol. 2002;13(s15):32-7
pubmed: 12688622
Lancet. 2020 May 30;395(10238):1695-1704
pubmed: 32401715
Blood. 2012 Jan 12;119(2):454-64
pubmed: 22096248
JAMA. 2020 Apr 28;323(16):1574-1581
pubmed: 32250385
JCI Insight. 2020 Jun 18;5(12):
pubmed: 32554924
Sci Immunol. 2018 Jan 26;3(19):
pubmed: 29374079
N Engl J Med. 2020 Nov 26;383(22):2184-2185
pubmed: 33147384
J Allergy Clin Immunol. 2020 Aug;146(2):270-272
pubmed: 32333916
Respir Med. 2007 Sep;101(9):1845-63
pubmed: 17544265
Int J Biol Sci. 2020 Mar 15;16(10):1724-1731
pubmed: 32226290
J Pediatr. 2003 Nov;143(5 Suppl):S118-26
pubmed: 14615710
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Lancet. 2020 May 30;395(10238):1670-1671
pubmed: 32401712
J Allergy Clin Immunol. 2020 Jul;146(1):110-118
pubmed: 32294485
Nat Med. 2006 Sep;12(9):1023-6
pubmed: 16906156
J Interferon Cytokine Res. 2004 Aug;24(8):439-54
pubmed: 15320958
Lancet. 2002 Mar 9;359(9309):831-4
pubmed: 11897281
Science. 2020 Oct 23;370(6515):
pubmed: 32972995
Arch Intern Med. 2008 Dec 8;168(22):2405-14
pubmed: 19064822
Eur Respir J. 2020 Oct 8;56(4):
pubmed: 32513781
Lancet Respir Med. 2014 Aug;2(8):621-30
pubmed: 24835835
Lancet. 2020 Mar 14;395(10227):846-848
pubmed: 32151325
Nat Med. 2009 Aug;15(8):955-9
pubmed: 19597505
Curr Opin Virol. 2016 Feb;16:15-23
pubmed: 26590692
J Infect Dis. 2014 Jul 15;209 Suppl 3:S93-9
pubmed: 24966196
J Biol Chem. 2020 Oct 9;295(41):13958-13964
pubmed: 32587093
EBioMedicine. 2020 Apr;54:102734
pubmed: 32279057
Front Immunol. 2019 Jan 15;9:3167
pubmed: 30705679
Science. 2020 Oct 23;370(6515):
pubmed: 32972996
Lancet. 2017 Sep 2;390(10098):946-958
pubmed: 28689664
Nature. 2020 Aug;584(7821):430-436
pubmed: 32640463
J Allergy Clin Immunol. 2012 Jun;129(6):1506-1514.e6
pubmed: 22657407
Vaccine. 2008 Jul 4;26(29-30):3551-5
pubmed: 18524433
Respir Res. 2010 Dec 31;11:184
pubmed: 21194432
Virology. 2009 Feb 5;384(1):209-15
pubmed: 19059617
Arch Dis Child. 2016 Feb;101(2):140-6
pubmed: 26342094
Am J Respir Crit Care Med. 2014 Jul 15;190(2):145-54
pubmed: 24937476
J Immunol. 2006 Aug 15;177(4):2088-96
pubmed: 16887967
Clin Rev Allergy Immunol. 2013 Dec;45(3):331-79
pubmed: 23575961
Am J Respir Crit Care Med. 2018 May 15;197(10):1265-1274
pubmed: 29466680
Scand J Infect Dis. 2004;36(1):31-6
pubmed: 15000556
Lancet Infect Dis. 2018 Nov;18(11):1191-1210
pubmed: 30243584
Nature. 2020 Dec;588(7837):315-320
pubmed: 32846427
J Allergy Clin Immunol. 2014 Jul;134(1):228-30
pubmed: 24636083
Eur J Pediatr. 2020 May;179(5):791-799
pubmed: 31912234
Nat Commun. 2018 Jun 8;9(1):2229
pubmed: 29884817
Lancet Respir Med. 2021 Feb;9(2):196-206
pubmed: 33189161
J Immunol. 2014 Dec 1;193(11):5444-52
pubmed: 25339659
Science. 2020 Aug 7;369(6504):718-724
pubmed: 32661059
BMJ. 2020 May 22;369:m1985
pubmed: 32444460
J Exp Med. 2005 Mar 21;201(6):937-47
pubmed: 15781584
Antimicrob Agents Chemother. 2020 Aug 20;64(9):
pubmed: 32661006
Nature. 2020 Mar;579(7798):265-269
pubmed: 32015508