Unknown

Dataset Information

0

MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier.


ABSTRACT:

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.

SUBMITTER: McGuckin MA 

PROVIDER: S-EPMC10630632 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier.

McGuckin Michael A MA   Davies Julie M JM   Felgner Pascal P   Wong Kuan Yau KY   Giri Rabina R   He Yaowu Y   Moniruzzaman Md M   Kryza Thomas T   Sajiir Haressh H   Hooper John D JD   Florin Timothy H TH   Begun Jakob J   Oussalah Abderrahim A   Hasnain Sumaira Z SZ   Hensel Michael M   Sheng Yong H YH  

Cellular and molecular gastroenterology and hepatology 20230901 6


<h4>Background & aims</h4>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.<h4>Methods</h4>Muc13<sup>-/-</sup> 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  ...[more]

Similar Datasets

| S-EPMC3811786 | biostudies-literature
| S-EPMC4100478 | biostudies-literature
| S-EPMC3397338 | biostudies-literature
| S-EPMC1913485 | biostudies-literature
| S-EPMC2898360 | biostudies-literature
2024-02-19 | PXD029606 | Pride
| S-EPMC11906825 | biostudies-literature
| S-EPMC7248004 | biostudies-literature
| S-EPMC9325389 | biostudies-literature
| S-EPMC5141278 | biostudies-literature