Clostridioides difficile Binary Toxin Is Recognized by the Toll-Like Receptor 2/6 Heterodimer to Induce a Nuclear Factor-κB Response.


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
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

1296-1300

Subventions

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

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Auteurs

Morgan Simpson (M)

Department of Pathology, University of Virginia, Charlottesville, Virginia, USA.

Alyse Frisbee (A)

Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.

Pankaj Kumar (P)

Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA.

Carsten Schwan (C)

Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Klaus Aktories (K)

Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

William A Petri (WA)

Department of Pathology, University of Virginia, Charlottesville, Virginia, USA.
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.

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Classifications MeSH