Summary of the article Muc2 Protects against Lethal Infectious Colitis by Disassociating pathogenic and Commensal Bacteria from the Colonic Mucosa

Investigation of the manner by which host cells evade the attack of attaching and effacing (AE) Escherichia coli pathogens was sought to be executed in this paper by analyzing the role of goblet cell-derived Muc2 in host-pathogen interactions. To accomplish the goal of this paper, Citrobacter rodentium, a murine AE pathogen related to AE coli, was inoculated to Muc2 deficient mice (Muc2--). Mice with Muc2 or the wild types were also infected with C. rodentium, and were used as control organisms. Physical and physiological changes were monitored, compared, and evaluated. Results showed that WT mice tend to release significant amount of Muc2 when exposed to pathogens as compared to Muc2-- mice thereby suggesting the importance of Muc2 in pathogen evasion. Further studies confirmed that Muc2 limits overall pathogen and commensal species in order to protect the host from prolonged bacterial AE infection.  

Enteropathogenic Escherichia coli (EPEC) and Enterohemorrhagic E. coli (EHEC), both of which are attaching and effacing (AE) types, are the main cause of mortality and morbidity in both developing and developed countries (Bergstrom et al., 2010). These microorganisms mainly target  the digestive system of patients and results to diarrhea, dehydration and a series of other complications. Aside from this, EHEC may also lead to the production of the highly lethal Shiga Toxin (Stx) if not properly treated. Main sources of these microorganisms are infected food and water supplies. Because of the profound significance of AE E. coli in public health, researchers are working hard to investigate the mechanisms by which hosts will be able to fight the detrimental to lethal effects of EHEC and EPEC. However, due to ethical reasons, actual tests on humans cannot be done so scientists opt to investigate the AE pathogen equivalent of E. coli on mice, Citrobacter rodentium (Bergstrom et al., 2010). This microorganism has been found to result to acute colitis, mucosal hyperplasia, barrier disruption and loose stools. Furthermore, a number of scientific studies have suggested that mucin production is one of the most important strategies of host cells when managing enteric bacterial infections.

Mucins are glycoproteins with high molecular weights and are embedded with serine, threonine, and proline-rich domains. One of its derivative, Muc1, was found to be active against Campylobacter jejuni infection by reducing the impact of the attack and prohibiting potential spread of the infectious agents (McAuley et al., (2007). In this study, Muc2, the major secretory mucin in both humans and mice, will be investigated. Muc2 forms polymers which become the basis of  two-distinct layers in the mammalian colon, inner and outer, where the former is sterile while the latter is heavily colonized by commensal bacteria (Bergstrom et al., 2010). Related researchers have confirmed the role of Muc2 in regulating commensal and gut homeostasis but its interaction with the mucosal pathogens is not yet established. In line with this, the authors of this study wanted to investigate the role of Muc2 in preventing the colonization of AE pathogens in the mucus layer by using C. rodentium in mice models.

Research DesignMethods
Experimental procedures made use of two groups of six to 11 weeks old mice where one group was composed of in vivo-altered Muc2 deficient (Muc2--) and the other included wild type (Muc2) mice. C. rodentium were inoculated to mice by oral gavage. Infected and uninfected tissues of the halothane-anesthetized and cervical dislocation-killed mice were collected and enumerated for bacterial counts. Histological staining and RNA extraction were performed on the tissues followed by cecal loop modeling, bioluminescent imaging, metabolic labeling, permeability and antimicrobial assay, DNA staining, and finally, statistical analysis of the measurements obtained.  

Results and Discussion
Results showed that Muc2-- mice exhibited increased susceptibility to C. rodentium, worsened mucosal damage, and elevated microcolony formation on their mucosal surface as compared to wild type mice. Also, mucus secretion was also significantly elevated in response to C. rodentium infection. These findings are consistent with the hypothesis that mucins play important role in the evasion of AE pathogens and it was discovered in this paper that the muc2 is the first line of defense of hosts against invading AE pathogens. It was also discovered that an array of non-pathogenic microorganisms have thrived in the gut of Muc2 deficient mice, an event that was not observed in wild type mice. Hence, the authors concluded that Muc2 in mammals serve an important role in effectively managing infectious and non-infectious agents by reducing commensal load on the mucosal surface.  

Presentation of my understanding of the paper
The findings presented in this paper offer a possible method of combating attaching and effacing EPEC and EHEC. Utilization of this knowledge may help researchers to finally devise a way to reduce, if not totally eliminate, the occurrence of digestive diseases related to E.coli infections in both developing and developed countries. Subsequent studies must be done to demonstrate Muc2 responses in humans. But at present, it can be said that this study, once perfected, will truly benefit humans and will offer a possible way of controlling disease proliferation. The authors must be commended for doing a detailed experiment and for presenting their results in a well-written report. Lastly, studies of this type must be executed more often in order to address the growing number of deaths due to bacterial infections.


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