Clostridioides difficile Binary Toxin Is Recognized by the Toll-Like Receptor 2/6 Heterodimer to Induce a Nuclear Factor-κB Response.
Clostridioides difficile
CDT
NF-κB
TLR2
TLR6
binary toxin
immune response
innate immunity
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
01 04 2022
01 04 2022
Historique:
received:
01
06
2020
accepted:
29
09
2020
pubmed:
5
10
2020
medline:
6
4
2022
entrez:
4
10
2020
Statut:
ppublish
Résumé
Clostridioides difficile infection (CDI) represents a significant burden on the health care system, one that is exacerbated by the emergence of binary toxin (CDT)-producing hypervirulent C. difficile strains. Previous work from our laboratory has shown that Toll-like receptor 2 (TLR2) recognizes CDT to induce inflammation. Here we explore the interactions of CDT with TLR2 and the impact on host immunity during CDI. We found that the TLR2/6 heterodimer, not TLR2/1, is responsible for CDT recognition, and that gene pathways including nuclear factor-κB and MAPK downstream of TLR2/6 are upregulated in mice with intact TLR2/6 signaling during CDI.
Identifiants
pubmed: 33011801
pii: 5917760
doi: 10.1093/infdis/jiaa620
pmc: PMC8974845
doi:
Substances chimiques
Antibodies, Bacterial
0
NF-kappa B
0
Tlr2 protein, mouse
0
Tlr6 protein, mouse
0
Toll-Like Receptor 2
0
Toll-Like Receptor 6
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1296-1300Subventions
Organisme : NIAID NIH HHS
ID : R01 AI124214
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI152477
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007496
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
Genes Dev. 2009 Oct 15;23(20):2376-81
pubmed: 19833765
Front Immunol. 2012 Apr 18;3:79
pubmed: 22566960
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nat Commun. 2019 Jun 20;10(1):2712
pubmed: 31221971
Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16422-7
pubmed: 21930894
PLoS Pathog. 2009 Oct;5(10):e1000626
pubmed: 19834554
Gut Microbes. 2014 Jan-Feb;5(1):15-27
pubmed: 24253566
Nat Microbiol. 2016 Jul 11;1(8):16108
pubmed: 27573114
Cell Host Microbe. 2019 May 8;25(5):756-765.e5
pubmed: 31003940
Emerg Infect Dis. 2011 Jun;17(6):976-82
pubmed: 21749757
Nucleic Acids Res. 2013 Jan;41(Database issue):D793-800
pubmed: 23143270
Cell Host Microbe. 2008 Oct 16;4(4):350-61
pubmed: 18854239
Mucosal Immunol. 2014 Sep;7(5):1266-77
pubmed: 24670426
N Engl J Med. 2015 Feb 26;372(9):825-34
pubmed: 25714160