Interleukin 4 induces rapid mucin transport, increases mucus thickness and quality and decreases colitis and Citrobacter rodentium in contact with epithelial cells
Journal article, 2019

Citrobacter rodentium infection is a murine model for pathogenic intestinal Escherichia coli infection. C. rodentium infection causes an initial decrease in mucus layer thickness, followed by an increase during clearance. We aimed to identify the cause of these changes and to utilize this naturally occurring mucus stimulus to decrease pathogen impact and inflammation. We identified that mucin production and speed of transport from Golgi to secretory vesicles at the apical surface increased concomitantly with increased mucus thickness. Of the cytokines differentially expressed during increased mucus thickness, IFN-γ and TNF-α decreased the mucin production and transport speed, whereas IL-4, IL-13, C. rodentium and E. coli enhanced these aspects. IFN-γ and TNF-α treatment in combination with C. rodentium and pathogenic E. coli infection negatively affected mucus parameters in vitro, which was relieved by IL-4 treatment. The effect of IL-4 was more pronounced than that of IL-13, and in wild type mice, only IL-4 was present. Increased expression of Il-4, Il-4-receptor α, Stat6 and Spdef during clearance indicate that this pathway contributes to the increase in mucin production. In vivo IL-4 administration initiated 10 days after infection increased mucus thickness and quality and decreased colitis and pathogen contact with the epithelium. Thus, during clearance of infection, the concomitant increase in IL-4 protects and maintains goblet cell function against the increasing levels of TNF-α and IFN-γ. Furthermore, IL-4 affects intestinal mucus production, pathogen contact with the epithelium and colitis. IL-4 treatment may thus have therapeutic benefits for mucosal healing.

Citrobacter rodentium


A/E pathogen




host-pathogen interaction





S. Sharba

University of Gothenburg

N. Navabi

University of Gothenburg

M. Padra

University of Gothenburg

J. A. Persson

University of Gothenburg

M. P. Quintana-Hayashi

University of Gothenburg

J. K. Gustafsson

University of Gothenburg

L. Szeponik

University of Gothenburg

V. Venkatakrishnan

University of Gothenburg

Åsa Sjöling

Karolinska University Hospital

Staffan Nilsson

University of Gothenburg

Chalmers, Mathematical Sciences, Applied Mathematics and Statistics

M. Quiding-Järbrink

University of Gothenburg

M. E.V. Johansson

University of Gothenburg

S. K. Linden

University of Gothenburg


2150-5594 (ISSN) 2150-5608 (eISSN)

Vol. 10 1 97-117

Subject Categories


Immunology in the medical area

Microbiology in the medical area





More information

Latest update