Epithelial cell types and their proposed roles in maintaining the mucosal barrier in human chagasic–megacolonic mucosa

Abstract

Patients suffering from chagasic megacolon must have an intact mucosal barrier as they survive this chronic disease for decades. A key structure of the mucosal barrier are epithelial cells. Vasoactive-intestinal-peptide (VIP)-positive nerve fibres are involved in influencing, e.g., epithelial cell proliferation, mucus secretion (e.g., mucin 2 and trefoil factor 3 of goblet cells) and inflammation or autoimmunity, all putative and/or known factors altered in chagasic megacolon. We analyzed qualitatively and quantitatively goblet cells, their specific markers, such as mucin 2 (MUC2) and trefoil factor 3 (TFF3) and enterocytes, the relation of VIP-immunoreactive nerve fibres to the epithelia, the distribution of gelsolin, a protein involved in chronic inflammation processes in the epithelia, and the proliferation rate of epithelial cells by combined 4',6-diamidino-2-phenylindole (DAPI) and phosphohistone-H3 (PHH3) staining. Goblet cells were the dominating epithelial cell type. They accounted for 38.4% of all epithelial cells in controls and changed to 58.9% in the megacolonic parts. In contrast to the overall expression in goblet cells of control epithelia, TFF3 was confined to goblet cells at the base of the crypts whereas MUC2 was found only in luminal goblet cells. Gelsolin-positive goblet cells were predominantly recognized within the controls. Finally, the mean value of mitosis increased from 1.5% within the controls up to 2.6% in the anal parts of the chagasic sepcimens. Taken together, increased cell proliferation, preponderance of goblet cells, differential MUC 2, and TFF 3 expression might all be factors maintaining an intact mucosal barrier within chagasic megacolon.

Phospho-proteomic analysis of primary human colon epithelial cells during the early Trypanosoma cruzi infection phase

“…Furthermore, increased TSP-1 expression induced by increased p-c-Jun can lead to a fibrogenic response which can cause colon pathology that could be implicated in the onset of megacolon. Fibrogenesis, due increased deposition of TSP-1, can lead to a marked thickening of the colon epithelium as observed in tissue sections of specimens from chagasic megacolon patients compared to controls [ 59 ]. Overall, we conclude that the colocalization of upregulated p-c-Jun and p-CREB is a putative key feature in T .…”

In focus in HCB

“…Patients suffering from chagasic megacolon have an intact mucosal barrier, and while the selective survival of VIP-ergic nerve fibres within the lamina propria has been demonstrated, a loss of cholinergic neurons occurs in the myenteric and submucosal plexus (Jabari et al 2014a, b). In the present investigation Koch et al (2017) have analyzed goblet cells [including their markers mucin 2 (MUC2) and trefoil factor 3 (TFF3)], as well as enterocytes, and the relation of VIPimmunoreactive fibers to these epithelial cell types. Goblet cells accounted for 38.4% of all epithelial cells in normal colon, and increased to 58.9% in chagasic-megacolonic mucosa.…”

Immunological Challenges to the Development of Chagasic Mega Syndromes

“…Therefore, it is common, in the same ganglion, the existence of neurons, sometimes deeply damaged alongside others morphologically intact. In severe cases, the lesion may be diffuse and the ganglion ends up being replaced by dense fibrous connective tissue [4]. It is permissible to admit a progression of the lesions of the plexus, which worsen proportionally to the duration and degree of the mega.…”