Interleukin 10-Deficient Mice Exhibit Defective Colonic Muc2 Synthesis Before and After Induction of Colitis by Commensal Bacteria

Abstract

Germ-free (GF) interleukin 10-deficient (IL-10) mice develop chronic colitis after colonization by normal enteric bacteria. Muc2 is the major structural component of the protective colonic mucus. Our aim was to determine whether primary or induced aberrations in Muc2 synthesis occur in GF IL-10 mice that develop colitis after bacterial colonization. GF IL-10 and wild-type mice were colonized with commensal bacteria for various intervals up to 6 weeks. Colitis was quantified by histologic score and IL-12 secretion. Muc2 synthesis, total level of Muc2, and Muc2 sulfation were measured quantitatively. GF IL-10 mice showed 10-fold lower Muc2 synthesis and Muc2 levels compared with GF wild-type mice, but Muc2 sulfation was not different. When bacteria were introduced, IL-10 mice developed colitis, whereas wild-type mice remained healthy. Muc2 synthesis was unchanged in wild-type mice, but IL-10 mice showed a peak increase in Muc2 synthesis 1 week after bacterial introduction, returning to baseline levels after 2 weeks. Total Muc2 levels decreased 2-fold in wild-type mice but remained at stable low levels in IL-10 mice. Upon introducing bacteria, Muc2 sulfation increased 2-fold in wild-type mice, whereas in IL-10 mice Muc2 sulfation decreased 10-fold. In conclusion, a primary defect in colonic Muc2 synthesis is present in IL-10 mice, whereas bacterial colonization and colitis in these mice led to reduced Muc2 sulfation. These quantitative and structural aberrations in Muc2 in IL-10 mice likely reduce the ability of their mucosa to cope with nonpathogenic commensal bacteria and may contribute to their susceptibility to develop colitis.

Mucin-bacterial interactions in the human oral cavity and digestive tract

“…The epithelium of germ-free mice differs morphologically from that of conventionally raised animals: non-degraded mucin is found in feces, their goblet cells are smaller and less abundant, the colonic mucus layer is approximately two times thicker and the weight of the cecum can reach up to eight times that of conventional animals. [81][82][83][84] The swelling of the cecum in germ-free animals is due to the accumulation of mucus, and the resulting retention of water, due to the absence of mucin-degrading bacteria. 85 In addition, when fecal suspensions or pure cultures of Clostridium, Bacteroides or Peptococcus were introduced into germ-free rodents, the cecum showed a striking reduction to its normal weight, 86,87 suggesting the beneficial workings of mucin-degrading bacteria.…”

“…In the study of Schwerbrock et al on the conventionalization of germ-free mice, the intestinal production of the major intestinal mucin Muc2 was carefully characterized and quantified as a function of time after colonization. 82 In healthy control mice the level of Muc2 production was steady after the conventionalization, however over time there was a However, as comparative studies on the efficiency of probiotic strains are scarce, the validation of this attribute has to be confirmed. For this type of study, the proper procedure would be to isolate the genuine mucin(s) from the organ of interest.…”

Resistance of C57BL/6 Mice to Amoebiasis Is Mediated by Nonhemopoietic Cells but Requires Hemopoietic IL-10 Production

“…We next examined the outcome of infection in IL-10 Ϫ/Ϫ mice on the resistant C57BL/6 background, because these mice acquire abundant defects in their epithelium (13,14,(21)(22)(23). When sacrificed at 9 -10 days postchallenge, B6 IL-10-deficient mice exhibited a significantly higher amoeba score, inflammation score, and culturepositive rate than their WT counterparts (Fig.…”

Fulminant Amoebic Colitis: Role of the Innate and Adaptive Immune Responses

“…In different experimental models, an important role has been suggested for IL-10 in the stimulation of innate resistance to E. histolytica infection, although the possible mechanisms are still unknown (Hamano et al, 2006). One possible mechanism could be the participation of IL-10 in the stimulation of the production of mucous by goblet cells in the epithelium (Schwerbrock et al, 2004), which in turn maintains the protective mucous barrier. Another possible mechanism is based on the immunosuppressive effects of IL-10 from epithelial cells on leukocytes (García-Zepeda et al, 2007).…”