Figure 11. Proposed model of the role of Muc2 in the disassociation of A/E pathogen and commensal bacteria from the large intestinal mucosa.

A. In a Muc2-sufficient intestine, A/E bacteria such as C. rodentium (yellow) need to first traverse the outer and inner mucus layers to access the underlying epithelium. Following infection of epithelial cells, there is an enhancement in mucin secretion probably due to synergistic actions between bacterial products and host derived cytokines after innate recognition by pattern recognition receptors, and recruitment of inflammatory cells such as PMNs. In addition, there is moderate epithelial barrier dysfunction as a result of host and pathogen induced alteration of tight junctions. As the A/E pathogen replicates following intimate attachment, the secreted Muc2 binds newly reproduced bacteria and flushes them away from the surface to prevent microcolony formation on the surface and their translocation into the mucosa. B. In a state of Muc2-deficiency the lack of mucus causes a more rapid infection and an accumulation of pathogens that are loosely associated with the mucosa, forming microcolonies. Commensal bacteria (red) can also be caught up in these pathogenic microcolonies, further increasing total burden at the surface and likelihood of direct and/or indirect epithelial damage. Following infection, severe barrier dysfunction occurs, mostly by altered tight junctions as well as overt epithelial cell death. As a result both the loosely-adherent pathogens and commensals leak across the epithelia and into the mucosa, overwhelming the phagocytes and perpetuating a vicious inflammatory cycle.