Human gut microbiota stimulate defined innate immune responses that vary from phylum to strain.
TLR2
TLR4
Treg
dendritic cell
fecal microbiota transplantation
host-microbe
innate immunity
macrophage
microbiome
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
12 10 2022
12 10 2022
Historique:
received:
29
11
2021
revised:
10
06
2022
accepted:
15
08
2022
pubmed:
14
9
2022
medline:
18
10
2022
entrez:
13
9
2022
Statut:
ppublish
Résumé
The potential of commensal bacteria to modulate host immunity remains largely uncharacterized, largely due to the vast number of strains that comprise the human gut microbiota. We have developed a screening platform to measure the innate immune responses of myeloid cells to 277 bacterial strains isolated from the gut microbiota of healthy individuals and those with inflammatory bowel diseases. The innate immune responses to gut-derived bacteria are as strong as those toward pathogenic bacteria, and they vary from phylum to strain. Myeloid cells differentially rely upon innate receptors TLR2 or TLR4 to sense taxa, with differential sensing of Bacteroidetes and Proteobacteria that predict in vivo functions. These innate immune responses can be modeled using combinations of up to 8 Toll-like receptor (TLR) agonists. Furthermore, the immunogenicity of strains is stable over time and following fecal microbiota transplantation into new human recipients. Collectively, this high-throughput approach provides an insight into how commensal microorganisms shape innate immune phenotypes.
Identifiants
pubmed: 36099923
pii: S1931-3128(22)00408-5
doi: 10.1016/j.chom.2022.08.009
pmc: PMC9588646
mid: NIHMS1835732
pii:
doi:
Substances chimiques
Toll-Like Receptor 2
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1481-1498.e5Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK112978
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123749
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124133
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM146636
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Author contributions M.P.S., G.J.B., and J.J.F. wrote the manuscript. M.P.S., S.S., G.J.B., Z.L., and I.M. collected the samples and performed the experiments. M.P.S., S.S., C.Y., S.M., G.J.B., and J.J.F. analyzed and interpreted the data. All authors read, provided critical feedback and approved the final manuscript. Declaration of interests J.J.F. is on the scientific advisory board of Vedanta Biosciences, reports receiving research grants from Janssen Pharmaceuticals and reports receiving consulting fees from Innovation Pharmaceuticals, Janssen Pharmaceuticals, BiomX and Vedanta Biosciences.
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