Intestinal Macromolecular Transport Supporting Adaptive Immunity

Abstract

The gastrointestinal tract performs opposing functions of nutrient absorption, barrier maintenance, and the delivery of luminal substances for the appropriate induction of tolerogenic or protective adaptive immunity. The single-layer epithelium lining the gastrointestinal tract is central to each of these functions by facilitating the uptake and processing of nutrients, providing a physical and chemical barrier to potential pathogens, and delivering macromolecular substances to the immune system to initiate adaptive immune responses. Specific transport mechanisms allow nutrient uptake and the delivery of macromolecules to the immune system while maintaining the epithelial barrier. This review examines historical observations supporting macromolecular transport by the intestinal epithelium, recent insights into the transport of luminal macromolecules to promote adaptive immunity, and how this process is regulated to promote appropriate immune responses. Understanding how luminal macromolecules are delivered to the immune system and how this is regulated may provide insight into the pathophysiology of inflammatory diseases of the gastrointestinal tract and potential preventative or therapeutic strategies.

Goblet cell associated antigen passages support the induction and maintenance of oral tolerance

“…Several routes by which luminal substances cross the epithelium have been identified including paracellular leak, the direct capture by LP-APCs via extension of trans-epithelial dendrites (TEDs) into the gut lumen, passage from the lumen via villous M cells, and passage from the lumen via goblet cell associated antigen passages (GAPs). [15][16][17][18][19][20][21][22] Of these, LP-APC extension of TEDs is the currently favored route to support the induction and maintenance of tolerance to luminal substances in the steady state, as the extension of TEDs does not compromise the epithelial barrier and would allow direct acquisition of luminal antigens by LP-APCs. 16 However, this process directly exposes the LP-APCs to luminal contents, which in vitro studies indicate induces mixed Th1 and Th2 responses.…”

Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut

“…By contrast, in the GI tract of zebrafish and suckling stage mammals, proteins are not fully digested in the lumen because of low protease activity (Henning, 1985;Robberecht et al, 1971;Rombout et al, 1985;Zhang et al, 2005). This allows antigens and maternal antibodies to be preserved and thus contribute to the development of innate and adaptive immune systems (Kulkarni and Newberry, 2019;Reinhardt, 1984). However, this feature of the immature vertebrate gut also presents a nutritional challenge and highlights the need for an alternative mechanism mediating dietary protein absorption.…”

Stages of Gut Development as a Useful Tool to Prevent Gut Alterations in Piglets

“…The specific transport of macromolecules comes cross the epithelium through M cells, which are specialized cells, active in the transcytosis process, a cellular specialization for transport of molecules across the mucosal barrier to the submucosal tissues. [ 18 ]. At the same time, tissue-specific activities of brush-border enzymes appear, with a low maltase and high lactase activities [ 14 ].This may partly be due to increased ingestion of amniotic fluid, as suggested by [ 15 ].…”