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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(...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
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.
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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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