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Updated: May 23, 2026

Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Axin1 prevents Salmonella invasiveness and inflammatory response in intestinal epithelial cells
Yong-guo Zhang1, Shaoping Wu, Yinglin Xia
1Department of Biochemistry, Rush University Medical Center, Chicago, Illinois, United States of America.
Background:
Axin1 and its homolog Axin2 are scaffold proteins essential for regulating Wnt signaling. Axin-dependent regulation of Wnt is important for various developmental processes and human diseases. However, the involvement of Axin1 and Axin2 in host defense and inflammation remains to be determined.
Methods/Principal Findings:
Here, we report that Axin1, but not Axin2, plays an essential role in host-pathogen interaction mediated by the Wnt pathway. Pathogenic Salmonella colonization greatly reduces the level of Axin1 in intestinal epithelial cells. This reduction is regulated at the posttranslational level in early onset of the bacterial infection. Further analysis reveals that the DIX domain and Ser614 of Axin1 are necessary for the Salmonella-mediated modulation through ubiquitination and SUMOylation.
Conclusion/Significance:
Axin1 apparently has a preventive effect on bacterial invasiveness and inflammatory response during the early stages of infection. The results suggest a distinct biological function of Axin1 and Axin2 in infectious disease and intestinal inflammation while they are functionally equivalent in developmental settings.
Insights
Axin1, a Wnt signaling protein, protects against bacterial infection and inflammation. Salmonella infection reduces Axin1 levels, impacting host defense mechanisms.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Axin1 and Axin2 are crucial scaffold proteins regulating Wnt signaling.
- Wnt pathway regulation is vital in development and disease.
- The role of Axin1 and Axin2 in host defense and inflammation is largely unknown.
Purpose of the Study:
- To investigate the involvement of Axin1 and Axin2 in host defense against bacterial pathogens.
- To elucidate the role of Axin1 in Wnt-mediated host-pathogen interactions.
Main Methods:
- Studied host-pathogen interactions mediated by the Wnt pathway.
- Analyzed Axin1 levels in intestinal epithelial cells during Salmonella infection.
- Investigated posttranslational modifications (ubiquitination and SUMOylation) affecting Axin1.
Main Results:
- Axin1, not Axin2, is essential for Wnt-mediated host-pathogen interactions.
- Salmonella infection significantly reduces intestinal epithelial Axin1 levels.
- Salmonella-induced Axin1 reduction involves ubiquitination and SUMOylation at the DIX domain and Ser614.
Conclusions:
- Axin1 plays a preventive role against bacterial invasiveness and inflammation in early infection stages.
- Axin1 and Axin2 exhibit distinct functions in infectious disease and inflammation, unlike their equivalent roles in development.
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