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

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...

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Autores principales: Simpson, Morgan, Frisbee, Alyse, Kumar, Pankaj, Schwan, Carsten, Aktories, Klaus, Petri, William A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Major Articles and Brief Reports
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974845/
https://www.ncbi.nlm.nih.gov/pubmed/33011801
http://dx.doi.org/10.1093/infdis/jiaa620
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author Simpson, Morgan
Frisbee, Alyse
Kumar, Pankaj
Schwan, Carsten
Aktories, Klaus
Petri, William A
author_facet Simpson, Morgan
Frisbee, Alyse
Kumar, Pankaj
Schwan, Carsten
Aktories, Klaus
Petri, William A
author_sort Simpson, Morgan
collection PubMed
description 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.
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spelling pubmed-89748452022-04-04 Clostridioides difficile Binary Toxin Is Recognized by the Toll-Like Receptor 2/6 Heterodimer to Induce a Nuclear Factor-κB Response Simpson, Morgan Frisbee, Alyse Kumar, Pankaj Schwan, Carsten Aktories, Klaus Petri, William A J Infect Dis Major Articles and Brief Reports 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. Oxford University Press 2020-10-03 /pmc/articles/PMC8974845/ /pubmed/33011801 http://dx.doi.org/10.1093/infdis/jiaa620 Text en © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Articles and Brief Reports
Simpson, Morgan
Frisbee, Alyse
Kumar, Pankaj
Schwan, Carsten
Aktories, Klaus
Petri, William A
Clostridioides difficile Binary Toxin Is Recognized by the Toll-Like Receptor 2/6 Heterodimer to Induce a Nuclear Factor-κB Response
title Clostridioides difficile Binary Toxin Is Recognized by the Toll-Like Receptor 2/6 Heterodimer to Induce a Nuclear Factor-κB Response
title_full Clostridioides difficile Binary Toxin Is Recognized by the Toll-Like Receptor 2/6 Heterodimer to Induce a Nuclear Factor-κB Response
title_fullStr Clostridioides difficile Binary Toxin Is Recognized by the Toll-Like Receptor 2/6 Heterodimer to Induce a Nuclear Factor-κB Response
title_full_unstemmed Clostridioides difficile Binary Toxin Is Recognized by the Toll-Like Receptor 2/6 Heterodimer to Induce a Nuclear Factor-κB Response
title_short Clostridioides difficile Binary Toxin Is Recognized by the Toll-Like Receptor 2/6 Heterodimer to Induce a Nuclear Factor-κB Response
title_sort clostridioides difficile binary toxin is recognized by the toll-like receptor 2/6 heterodimer to induce a nuclear factor-κb response
topic Major Articles and Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8974845/
https://www.ncbi.nlm.nih.gov/pubmed/33011801
http://dx.doi.org/10.1093/infdis/jiaa620
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