The front line of enteric host defense against unwelcome intrusion of harmful microorganisms: mucins, antimicrobial peptides, and microbiota

Abstract

The intestinal tract is a complex ecosystem that combines resident microbiota and the cells of various phenotypes with complex metabolic activities that line the epithelial wall. The intestinal cells that make up the epithelium provide physical and chemical barriers that protect the host against the unwanted intrusion of microorganisms that hijack the cellular molecules and signaling pathways of the host and become pathogenic. Some of the organisms making up the intestinal microbiota also have microbicidal effects that contribute to the barrier against enteric pathogens. This review describes the two cell lineages present in the intestinal epithelium: the goblet cells and the Paneth cells, both of which play a pivotal role in the first line of enteric defense by producing mucus and antimicrobial peptides, respectively. We also analyze recent insights into the intestinal microbiota and the mechanisms by which some resident species act as a barrier to enteric pathogens. Moreover, this review examines whether the cells producing mucins or antimicrobial peptides and the resident microbiota act in partnership and whether they function individually and/or synergistically to provide the host with an effective front line of defense against harmful enteric pathogens.

Figures

FIG. 1.

Architecture of the intestinal epithelium lining the intestinal tract. (A) Crypt-villus cell organization. The cell renewall is achieved from the pluripotent intestinal stems cells are up from the crypt base in the small intestinal and at the crypt base in the colon. Epithelial cells migrate up the crypt where they perform their differentiation, acquiring specific intestinal functions of absorption and secretion. Three cell types differentiate as they migrate: the predominant enterocytes, the mucus-secreting Goblet cells, and the peptide hormone-secreting enteroendocrine cells. Oppositely, the Paneth cells migrate down to the base of the crypt. (B) The assembly of the polarized epithelial-cell types results from an epithelium that provides a permeability barrier between the external and internal compartments. This barrier function is assumed by the junctional domain, including well-defined gap junctions, desmosomes, adherens junctions, and tight junctions. Four polarized epithelial cell lineages were present in the intestinal epithelium: the enterocytes expressing at the apical domain a dense, well-ordered brush border consisting of organized microvilli in the membrane of which oriented proteins support specific functions; the mucus-secreting goblet cells (cell with large yellow granules) producing membrane-bound mucins and containing mature storage granules in which secreted mucins are packaged; the enteroendocrine cells (cells with small, dark granules) containing small, oriented secretory granules in which different peptide hormones should be stored, although a same granule may store more than one peptide hormone; and the Paneth cells (cell with small, red granules) containing apically oriented granules in which AMPs and antimicrobial proteins were packaged as pro or mature forms. Enteric pathogens (red bacteria with flagella) interact with the intestinal epithelial cells, enter the cells, affect the cell architecture or organization, and disturb the cell functions. The commensal bacteria (blue and green bacteria) mainly reside in the lumen outside the mucus layer. Secreted mucins (in yellow, coating the epithelial surface) in association with the membrane-bound mucins act as a physicochemical barrier for the protection of the epithelial cell surface against undesirable harmful pathogens.

FIG. 2.

The chemical front line of enteric host defense against unwelcome intrusion of harmful bacterial pathogens. Enteric invasive and noninvasive bacterial pathogens (red bacteria) expressing pathogenic factors (adhesive factors, invasines, and toxins, etc.) interact with the host epithelial cells lining the villi. At the base of the crypt, the Paneth cells containing antimicrobial-rich granules, released AMPs (red and yellow spike rings) upon exposure of intestinal epithelium to undesirable harmful pathogens and/or their bacterial products (LPS and toxins, etc.). Moreover, other intestinal cells lining the villi also secreted antimicrobial proteins (orange spike rings). In parallel, the commensal gram-negative (green bacteria) and gram-positive (blue bacteria) intestinal bacteria that reside in the lumen produced antibacterial molecules (green triangles and blue circles).