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.