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MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier
BACKGROUND & AIMS: MUC13 cell surface mucin is highly expressed on the mucosal surface throughout the intestine, yet its role against bacterial infection is unknown. We investigated how MUC13 impacts Salmonella typhimurium (S Tm) infection and elucidated its mechanisms of action. METHODS: Muc13(...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630632/ https://www.ncbi.nlm.nih.gov/pubmed/37660948 http://dx.doi.org/10.1016/j.jcmgh.2023.08.011 |
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author | McGuckin, Michael A. Davies, Julie M. Felgner, Pascal Wong, Kuan Yau Giri, Rabina He, Yaowu Moniruzzaman, Md Kryza, Thomas Sajiir, Haressh Hooper, John D. Florin, Timothy H. Begun, Jakob Oussalah, Abderrahim Hasnain, Sumaira Z. Hensel, Michael Sheng, Yong H. |
author_facet | McGuckin, Michael A. Davies, Julie M. Felgner, Pascal Wong, Kuan Yau Giri, Rabina He, Yaowu Moniruzzaman, Md Kryza, Thomas Sajiir, Haressh Hooper, John D. Florin, Timothy H. Begun, Jakob Oussalah, Abderrahim Hasnain, Sumaira Z. Hensel, Michael Sheng, Yong H. |
author_sort | McGuckin, Michael A. |
collection | PubMed |
description | BACKGROUND & AIMS: MUC13 cell surface mucin is highly expressed on the mucosal surface throughout the intestine, yet its role against bacterial infection is unknown. We investigated how MUC13 impacts Salmonella typhimurium (S Tm) infection and elucidated its mechanisms of action. METHODS: Muc13(-/-) and wild-type littermate mice were gavaged with 2 isogenic strains of S Tm after pre-conditioning with streptomycin. We assessed clinical parameters, cecal histology, local and systemic bacterial load, and proinflammatory cytokines after infection. Cecal enteroids and epithelial cell lines were used to evaluate the mechanism of MUC13 activity after infection. The interaction between bacterial SiiE and MUC13 was assessed by using siiE-deficient Salmonella. RESULTS: S Tm-infected Muc13(-/-) mice had increased disease activity, histologic damage, and higher local and systemic bacterial loads. Mechanistically, we found that S Tm binds to MUC13 through its giant SiiE adhesin and that MUC13 acts as a pathogen-binding decoy shed from the epithelial cell surface after pathogen engagement, limiting bacterial invasion. In addition, MUC13 reduces epithelial cell death and intestinal barrier breakdown by enhancing nuclear factor kappa B signaling during infection, independent of its decoy function. CONCLUSIONS: We show for the first time that MUC13 plays a critical role in antimicrobial defense against pathogenic S Tm at the intestinal mucosal surface by both acting as a releasable decoy limiting bacterial invasion and reducing pathogen-induced cell death. This further implicates the cell surface mucin family in mucosal defense from bacterial infection. |
format | Online Article Text |
id | pubmed-10630632 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-106306322023-09-01 MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier McGuckin, Michael A. Davies, Julie M. Felgner, Pascal Wong, Kuan Yau Giri, Rabina He, Yaowu Moniruzzaman, Md Kryza, Thomas Sajiir, Haressh Hooper, John D. Florin, Timothy H. Begun, Jakob Oussalah, Abderrahim Hasnain, Sumaira Z. Hensel, Michael Sheng, Yong H. Cell Mol Gastroenterol Hepatol Original Research BACKGROUND & AIMS: MUC13 cell surface mucin is highly expressed on the mucosal surface throughout the intestine, yet its role against bacterial infection is unknown. We investigated how MUC13 impacts Salmonella typhimurium (S Tm) infection and elucidated its mechanisms of action. METHODS: Muc13(-/-) and wild-type littermate mice were gavaged with 2 isogenic strains of S Tm after pre-conditioning with streptomycin. We assessed clinical parameters, cecal histology, local and systemic bacterial load, and proinflammatory cytokines after infection. Cecal enteroids and epithelial cell lines were used to evaluate the mechanism of MUC13 activity after infection. The interaction between bacterial SiiE and MUC13 was assessed by using siiE-deficient Salmonella. RESULTS: S Tm-infected Muc13(-/-) mice had increased disease activity, histologic damage, and higher local and systemic bacterial loads. Mechanistically, we found that S Tm binds to MUC13 through its giant SiiE adhesin and that MUC13 acts as a pathogen-binding decoy shed from the epithelial cell surface after pathogen engagement, limiting bacterial invasion. In addition, MUC13 reduces epithelial cell death and intestinal barrier breakdown by enhancing nuclear factor kappa B signaling during infection, independent of its decoy function. CONCLUSIONS: We show for the first time that MUC13 plays a critical role in antimicrobial defense against pathogenic S Tm at the intestinal mucosal surface by both acting as a releasable decoy limiting bacterial invasion and reducing pathogen-induced cell death. This further implicates the cell surface mucin family in mucosal defense from bacterial infection. Elsevier 2023-09-01 /pmc/articles/PMC10630632/ /pubmed/37660948 http://dx.doi.org/10.1016/j.jcmgh.2023.08.011 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Research McGuckin, Michael A. Davies, Julie M. Felgner, Pascal Wong, Kuan Yau Giri, Rabina He, Yaowu Moniruzzaman, Md Kryza, Thomas Sajiir, Haressh Hooper, John D. Florin, Timothy H. Begun, Jakob Oussalah, Abderrahim Hasnain, Sumaira Z. Hensel, Michael Sheng, Yong H. MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier |
title | MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier |
title_full | MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier |
title_fullStr | MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier |
title_full_unstemmed | MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier |
title_short | MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier |
title_sort | muc13 cell surface mucin limits salmonella typhimurium infection by protecting the mucosal epithelial barrier |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630632/ https://www.ncbi.nlm.nih.gov/pubmed/37660948 http://dx.doi.org/10.1016/j.jcmgh.2023.08.011 |
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