A new report in PLoS Pathogens by Bergstrom and colleagues provides a detailed look at the role of mucin 2 (MUC2) in protection against enteric pathogens.

 Localization of Citrobacter rodentium on the mucosal epithelium of a wild-type mouse (left panel) and a mucin 2-deficient mouse (right panel). Visualized are bacterial lipopolysaccharide (green), the secreted effector Tir (a marker for bacterial adherence) (red) and nuclei of host cells (blue). Image is reproduced, with permission, from Bergstrom, K. S. B. et al.

Mucins are high-molecular-mass glycoproteins that are produced by epithelial cells in secreted and membrane-bound forms. Previous studies have indicated that the absence of membrane-bound mucins exacerbates infection with enteric bacterial pathogens, but how secreted mucins protect the host remained unknown. In this study using Citrobacter rodentium , a common model organism for pathogenic Escherichia coli infections in mice, the authors investigated the role of the major colonic secretory mucin MUC2. MUC2 is synthesized by goblet cells in the intestinal epithelium, ultimately forming a mucus gel layer up to 800 μm thick. The authors found that C. rodentium was sporadically detected in the MUC2 layer of infected wild-type animals, indicating that the mucus layer must be penetrated by the pathogen. To confirm a protective function for MUC2, they showed that mice deficient in MUC2 (Muc2−/−) lost more weight, had an approximately fourfold higher mortality rate, displayed worsened colonic disease and harboured more total C. rodentium than wild-type mice.

Interestingly, the number of C. rodentium that adhered tightly to the epithelium was similar in Muc2−/− and wild-type mice, but the mutant mice harboured more pathogens in their intestinal lumen.

A closer look at the bacteria in the intestine revealed that in Muc2−/− mice C. rodentium formed microcolonies on the surface of the epithelium. Commensal bacteria could also be detected in these microcolonies, but they were not detected with the pathogen in wild-type mice. Therefore, MUC2 provides a barrier function that prevents commensal bacteria from interacting with the epithelium.

To determine how the lack of MUC2 results in increased pathogenesis, the authors tested which bacterial factors were required for infection. Interestingly, the type III secretion system (T3SS) effector EspF, an important virulence factor in infection of wild-type mice, was dispensable for infection of Muc2−/− mice, although the T3SS was required. In addition, more dextran passed across the epithelium in infected Muc2−/− mice than in uninfected Muc2−/− or wild-type mice. More bacteria penetrated the epithelium in Muc2−/− mice, leading to bacteraemia and C. rodentium infection of various organs, which is the likely cause of the increased mortality of the mutant. Therefore, MUC2 reduces the increased permeability of the intestinal epithelium that is induced by the pathogenic bacteria.

The total number of enteric bacteria was similar in uninfected wild-type and Muc2−/− mice; however, following infection with C. rodentium, the total level of commensal bacteria dropped in wild-type mice but not in mutant mice. Therefore, MUC2 probably protects the host by flushing out both commensal and pathogenic enteric bacteria during an infection.