Entamoeba histolytica Alters Ileal Paneth Cell Functions in Intact and Muc2 Mucin Deficiency

Abstract

Enteric α-defensins, termed cryptdins (Crps) in mice, and lysozymes secreted by Paneth cells contribute to innate host defense in the ileum. Antimicrobial factors including lysozymes and β-defensins are often embedded in luminal glycosylated colonic Muc2 mucin secreted by goblet cells that form the protective mucus layer critical in gut homeostasis and pathogen invasion. In this study we investigated ileal innate immunity against ), the causative agent of intestinal amebiasis, by inoculating parasites in closed ileal loops in and littermates and quantifying Paneth cell localization (lysozyme expression) and function (Crps secretion). Relative to littermates, showed disorganized mislocalization of Paneth cells that was diffusely distributed with elevated lysozyme secretion in the crypts and on villi in response to Inhibiting Gal-lectin binding with exogenous galactose andCP5- had no effect on parasite-induced erratic Paneth cell lysozyme synthesis. Although basal ileal expression of genes was unaffected in mice in response to there was robust release of pro-inflammatory cytokines and Crp peptide secretions in luminal exudates that was also present in the colon. Interestingly, secreted cysteine proteinases cleaved the pro-region of Crp 4 but not the active form. These findings define Muc2 mucin as an essential component of ileal barrier function that regulates localization and function of Paneth cells critical in host defense against microbes.

Impact of Autophagy of Innate Immune Cells on Inflammatory Bowel Disease

“…Subsequently, α-defensin, an antimicrobial peptide and an innate immune effector, was discovered within Paneth cell granules [118]. Paneth cells play an important role as intestinal epithelial cells responsible for innate immunity [119,120,121]. In Caucasians, abnormalities in the NOD2 gene, which was first identified as a CD susceptibility gene, inhibit α-defensin secretion by Paneth cells [122,123].…”

Host Protective Mechanisms to Intestinal Amebiasis

“…One of the first responses is by the goblet cells that produce mucins. In addition to mucin production, goblet cells can regulate Paneth cell morphology and function; it has been reported that, in Muc2 −/− mice, the localization of Paneth cells is altered and secretion of cathelicidin is decreased, while the secretion of α-defensins is increased [ 7 , 29 ]. Studies have revealed the amebicidal activity of α-defensins and β-defensins.…”

Ingested Engineered Nanomaterials Affect the Expression of Mucin Genes—An In Vitro-In Vivo Comparison

“…In addition, Muc2 deficiency has been connected to an aberrant inflammatory response including increased Il-8 release and to changes of metabolic pathways with an associated formation of preneoplastic lesions [82,83]. Muc2 deficient mice are more prone to ileal infections and develop spontaneous ileal tumors [40,41]. Hence, an ENM induced Muc2 downregulation might increase the susceptibility for such adverse outcomes.…”

“…In the course of intestinal inflammatory diseases, particularly the predominant gastric mucins MUC1 and MUC5AC, but also other mucins such as MUC20 were described to be differentially expressed [34][35][36]. The importance of the constitutive expression of mucins has been highlighted by mouse models deficient of MUC1, MUC2, and MUC13, revealing elevated susceptibilities towards intestinal infections, inflammations and spontaneous tumors [37][38][39][40][41][42].…”