Intrinsic Defense Mechanisms of the Intestinal Epithelium

Abstract

The intestinal epithelium is a single cell layer that facilitates the absorption of nutrients but also provides a tight barrier to prevent pathogen invasion and dissemination of commensal microbes. Specialized epithelial cells of the gastrointestinal tract achieve this frontline defense by working in concert with lymphoid, myeloid, and stromal cells to secrete an array of factors that limit direct contact between the epithelium and infectious agents. The importance of these mechanisms is underscored by the ability of enteric pathogens to target these mechanisms to achieve invasion and dissemination. This review highlights recent advances in our understanding of these intricate molecular and cellular mechanisms adopted by these cells to promote spatial segregation and barrier maintenance.

Figure 1. Specialized epithelial cell lineages promote barrier protection in the small intestine

Stem cells located in the crypts give rise to intestinal epithelial cells (IECs) with specialized function. Enterocytes predominate the single layer epithelium and participate in the exchange of nutrients. Paneth cells reside in the base of the crypts and secrete antimicrobial peptides, while other types of IECs migrate up the crypt-villus axis. Goblet cells produce mucins that form a physical barrier against invading pathogens and microbionts. Tuft cells secrete cytokines that help initiate immune responses to parasites. M cells line the Peyer’s patches and mediate transport of luminal antigens and bacteria to dendritic cells that initiate B and T cell responses, including production of a diverse repertoire of IgA by plasma cells in the lamina propria, the underlying connective tissue. IECs then transport IgA to the lumen with the polymeric IgA receptor (pIgR). IECs also stimulate cytokine production by innate lymphoid cells (ILCs) in response to adherent microbionts such as segmented filamentous bacteria (SFB), and produce many inflammatory mediators. The function of enteroendocrine cells (which secrete hormones) and other IECs like cup cells in host defense require investigation.