Antimicrobial overproduction sustains intestinal inflammation by inhibiting Enterococcus colonization.
NOD2
REG3
antimicrobial proteins
enterococci
inflammatory bowel disease
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
13 09 2023
13 09 2023
Historique:
received:
10
02
2023
revised:
02
07
2023
accepted:
07
08
2023
pmc-release:
13
09
2024
medline:
18
9
2023
pubmed:
1
9
2023
entrez:
31
8
2023
Statut:
ppublish
Résumé
Loss of antimicrobial proteins such as REG3 family members compromises the integrity of the intestinal barrier. Here, we demonstrate that overproduction of REG3 proteins can also be detrimental by reducing a protective species in the microbiota. Patients with inflammatory bowel disease (IBD) experiencing flares displayed heightened levels of secreted REG3 proteins that mediated depletion of Enterococcus faecium (Efm) from the gut microbiota. Efm inoculation of mice ameliorated intestinal inflammation through activation of the innate immune receptor NOD2, which was associated with the bacterial DL-endopeptidase SagA that generates NOD2-stimulating muropeptides. NOD2 activation in myeloid cells induced interleukin-1β (IL-1β) secretion to increase the proportion of IL-22-producing CD4
Identifiants
pubmed: 37652008
pii: S1931-3128(23)00327-X
doi: 10.1016/j.chom.2023.08.002
pmc: PMC10502928
mid: NIHMS1925597
pii:
doi:
Substances chimiques
Anti-Infective Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1450-1468.e8Subventions
Organisme : NIAID NIH HHS
ID : R01 AI130945
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI140754
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests K.C. has received research support from Pfizer, Takeda, Pacific Biosciences, Genentech, and Abbvie. K.C. has consulted for or received an honoraria from Puretech Health, Genentech, and Abbvie. K.C. is an inventor on U.S. patent 10,722,600 and provisional patent 62/935,035 and 63/157,225. H.C.H. has received research support from Rise Therapeutics and LISCure Biosciences. U.S. patents PCT/US16/28836 (H.C.H.) and PCT/US2020/019038 (H.C.H. and M.E.G.) were obtained for the commercial use of SagA-engineered bacteria. Rise Therapeutics has licensed these patents to develop SagA-probiotics as therapeutics. J.A. reports consultancy fees, honoraria, or advisory board fees from Abbvie, Adiso, Bristol Myers Squibb, Janssen, Pfizer, Fresnius, and BioFire Diagnostics.
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