Role of Intestinal Mucins in Innate Host Defense Mechanisms against Pathogens

Abstract

Gastrointestinal mucins produced by goblet cells comprise the main structural components of the mucus layer. Mucins play a critical role in the maintenance of mucosal homeostasis and are responsible for the differential effector and regulatory responses against a plethora of microorganisms, including commensals and pathogens. In this review, we present a comprehensive overview on mucin biology, its properties, classification and gene assembly. We also consider the structure of the mucin gene, its proteins and its role in innate host defenses. We compare the various mucin secretagogues and the differential regulatory pathways involved in mucin biosynthesis and secretion during normal and diverse pathogenic conditions. Finally, we summarize the putative uncharted aspects of mucin-derived innate host defenses, whose exploration will help drug developers to identify factors that can strengthen mucosal integrity and will facilitate basic science research into curative treatments for gastrointestinal diseases.

Dietary supplementation with ovine serum immunoglobulin is associated with an increased gut luminal mucin concentration in the growing rat

“…Intestinal goblet cells may increase their discharge of mucin in response to mucin secretagogue (such as prostaglandin E2, cholera toxin, interleukin (IL)-4, IL-6, interferon-g, tumor necrosis factor-a) stimulation by two processes and through the action of various secondary messengers such as intracellular Ca 21 , cAMP and diacylglycerol, which activates protein kinase C. In many mucus cells, a phenomenon of compound exocytosis is induced, resulting in deep cavitation of the apical membrane surface of mucus cells (Specian and Oliver, 1991;Forstner, 1995;Dharmani et al, 2009). Some intestinal goblet cells may also react to stimulation by way of a second process that decreases the intracellular store of mucus granules but without cavitation (Specian and Oliver, 1991;Forstner, 1995).…”

Muc-2–Deficient Mice Display a Sex-Specific, COX-2–Related Impairment of Gastric Mucosal Repair

“…[1][2][3][4] Mucins, the carbohydrate-rich glycoprotein building blocks of the mucus gel, determine both the thickness and the major properties of mucus. 6,7 There are 21 distinct mucin genes. 6 The Muc2 gene has been implicated as crucial in colonic mucosal defense, based on observations that Muc-2-deficient mice exhibit lowgrade mucosal inflammation in the basal state, and have an increased susceptibility to colitis.…”

“…6,7 There are 21 distinct mucin genes. 6 The Muc2 gene has been implicated as crucial in colonic mucosal defense, based on observations that Muc-2-deficient mice exhibit lowgrade mucosal inflammation in the basal state, and have an increased susceptibility to colitis. 11,22,29,30 MUC-2 is not a major form of mucin in the healthy stomach of humans or rodents, but has been shown to be expressed in gastric carcinoma.…”

“…5 A major component of mucus is mucin, synthesis of which is encoded by 21 different mucin (MUC) genes in humans, mouse, and rat. 6 These genes encode for both membrane-bound and secretory mucins. Mucin expression is cell-and tissue-specific.…”

A sticky end for gastrointestinal helminths; the role of the mucus barrier

“…There have been 18 family members identified in humans, which have orthologues in mice and a subset of these mucins are selectively expressed at different anatomical sites along the GI tract 18, 19, 20, 21. Mucins can further be classified into 2 major subtypes: transmembrane and secreted mucins.…”