Upper airway gene expression shows a more robust adaptive immune response to SARS-CoV-2 in children.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 07 2022
08 07 2022
Historique:
received:
05
08
2021
accepted:
31
05
2022
entrez:
8
7
2022
pubmed:
9
7
2022
medline:
14
7
2022
Statut:
epublish
Résumé
Unlike other respiratory viruses, SARS-CoV-2 disproportionately causes severe disease in older adults whereas disease burden in children is lower. To investigate whether differences in the upper airway immune response may contribute to this disparity, we compare nasopharyngeal gene expression in 83 children (<19-years-old; 38 with SARS-CoV-2, 11 with other respiratory viruses, 34 with no virus) and 154 older adults (>40-years-old; 45 with SARS-CoV-2, 28 with other respiratory viruses, 81 with no virus). Expression of interferon-stimulated genes is robustly activated in both children and adults with SARS-CoV-2 infection compared to the respective non-viral groups, with only subtle distinctions. Children, however, demonstrate markedly greater upregulation of pathways related to B cell and T cell activation and proinflammatory cytokine signaling, including response to TNF and production of IFNγ, IL-2 and IL-4. Cell type deconvolution confirms greater recruitment of B cells, and to a lesser degree macrophages, to the upper airway of children. Only children exhibit a decrease in proportions of ciliated cells, among the primary targets of SARS-CoV-2, upon infection. These findings demonstrate that children elicit a more robust innate and especially adaptive immune response to SARS-CoV-2 in the upper airway that likely contributes to their protection from severe disease in the lower airway.
Identifiants
pubmed: 35803954
doi: 10.1038/s41467-022-31600-0
pii: 10.1038/s41467-022-31600-0
pmc: PMC9263813
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3937Subventions
Organisme : NIAID NIH HHS
ID : T32 AI060537
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM141323
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007641
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL155418
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL138461
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2022. The Author(s).
Références
Clin Infect Dis. 2020 Jul 28;71(15):889-890
pubmed: 32215618
Acta Paediatr. 2020 Jun;109(6):1088-1095
pubmed: 32202343
Lancet. 2011 Dec 3;378(9807):1917-30
pubmed: 22078723
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
BMC Biotechnol. 2016 Jun 24;16(1):54
pubmed: 27342544
Nature. 2020 Aug;584(7821):430-436
pubmed: 32640463
Clin Infect Dis. 2020 Nov 19;71(16):2305-2306
pubmed: 32433729
Nature. 2022 Feb;602(7896):321-327
pubmed: 34937051
Nat Med. 2020 Apr;26(4):502-505
pubmed: 32284613
Euro Surveill. 2020 Aug;25(32):
pubmed: 32794447
Proc Natl Acad Sci U S A. 2018 Dec 26;115(52):E12353-E12362
pubmed: 30482864
Nature. 2020 Nov;587(7835):619-625
pubmed: 33208946
Am J Respir Cell Mol Biol. 2022 Feb;66(2):206-222
pubmed: 34731594
Nat Commun. 2021 Jul 29;12(1):4678
pubmed: 34326343
J Infect Dis. 2022 Feb 1;225(3):392-395
pubmed: 34850028
Nucleic Acids Res. 2019 Jul 2;47(W1):W199-W205
pubmed: 31114916
Nat Biotechnol. 2016 May;34(5):525-7
pubmed: 27043002
Sci Rep. 2021 Feb 4;11(1):3044
pubmed: 33542262
Nat Immunol. 2021 Jan;22(1):25-31
pubmed: 33154590
Lancet Child Adolesc Health. 2021 May;5(5):e12-e13
pubmed: 33713603
JAMA Pediatr. 2021 Feb 1;175(2):176-184
pubmed: 33226415
Nat Methods. 2015 May;12(5):453-7
pubmed: 25822800
Nature. 2021 Feb;590(7844):140-145
pubmed: 33137809
BMC Public Health. 2017 Mar 21;17(1):271
pubmed: 28320361
JAMA Pediatr. 2021 Oct 1;175(10):e212025
pubmed: 34115094
Pediatrics. 2020 Jun;145(6):
pubmed: 32179660
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
PLoS One. 2019 Jun 20;14(6):e0218318
pubmed: 31220115
Nat Biotechnol. 2022 Mar;40(3):319-324
pubmed: 34408314
JCI Insight. 2021 May 10;6(9):
pubmed: 33822777
Epidemiol Infect. 2020 Feb 13;148:e48
pubmed: 32052719
Pediatr Infect Dis J. 2007 Jan;26(1):68-74
pubmed: 17195709
F1000Res. 2015 Dec 30;4:1521
pubmed: 26925227
Lancet. 2017 Sep 2;390(10098):946-958
pubmed: 28689664
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
BMJ Open Respir Res. 2021 Feb;8(1):
pubmed: 33627333
Gigascience. 2020 Oct 15;9(10):
pubmed: 33057676
Nat Commun. 2020 Nov 17;11(1):5854
pubmed: 33203890
JAMA. 2021 Jan 12;325(2):123-124
pubmed: 33331845
N Engl J Med. 2021 Dec 23;385(26):2489-2491
pubmed: 34941024
Sci Transl Med. 2020 Oct 7;12(564):
pubmed: 32958614
Eur J Epidemiol. 2020 Dec;35(12):1123-1138
pubmed: 33289900
PLoS Biol. 2021 Mar 17;19(3):e3001143
pubmed: 33730024
Eur J Clin Microbiol Infect Dis. 2020 Jun;39(6):1059-1061
pubmed: 32342252
Expert Rev Anti Infect Ther. 2016 Oct;14(10):961-8
pubmed: 27560100
Cell Rep. 2021 Oct 5;37(1):109773
pubmed: 34587479
N Engl J Med. 2010 May 6;362(18):1708-19
pubmed: 20445182
Int J Pediatr Otorhinolaryngol. 2021 Mar;142:110626
pubmed: 33477014
Clin Microbiol Infect. 2021 Dec;27(12):1858.e1-1858.e7
pubmed: 34384874
PLoS Pathog. 2021 Jan 28;17(1):e1009292
pubmed: 33507952
Clin Infect Dis. 2021 Sep 15;73(6):e1384-e1386
pubmed: 33949655