Chylomicrons Promote Intestinal Absorption and Systemic Dissemination of Dietary Antigen (Ovalbumin) in Mice

Abstract

BackgroundA small fraction of dietary protein survives enzymatic degradation and is absorbed in potentially antigenic form. This can trigger inflammatory responses in patients with celiac disease or food allergies, but typically induces systemic immunological tolerance (oral tolerance). At present it is not clear how dietary antigens are absorbed. Most food staples, including those with common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides (LCT), which stimulate mesenteric lymph flux and postprandial transport of chylomicrons through mesenteric lymph nodes (MLN) and blood. Most dietary antigens, like ovalbumin (OVA), are emulsifiers, predicting affinity for chylomicrons. We hypothesized that chylomicron formation promotes intestinal absorption and systemic dissemination of dietary antigens.Methodology/Principal FindingsAbsorption of OVA into MLN and blood was significantly enhanced when OVA was gavaged into fasted mice together with LCT compared with medium-chain triglycerides (MCT), which do not stimulate chylomicron formation. The effect of LCT was blocked by the addition of an inhibitor of chylomicron secretion, Pluronic L-81. Adoptively transferred OVA-specific DO11.10 T-cells proliferated more extensively in peripheral lymph nodes when OVA was gavaged with LCT than with MCT or LCT plus Pluronic L-81, suggesting that dietary OVA is systemically disseminated. Most dietary OVA in plasma was associated with chylomicrons, suggesting that these particles mediate systemic antigen dissemination. Intestinal-epithelial CaCo-2 cells secreted more cell-associated, exogenous OVA when stimulated with oleic-acid than with butyric acid, and the secreted OVA appeared to be associated with chylomicrons.Conclusions/SignificancePostprandial chylomicron formation profoundly affects absorption and systemic dissemination of dietary antigens. The fat content of a meal may affect immune responses to dietary antigens by modulating antigen absorption and transport.

Impairments in the intrinsic contractility of mesenteric collecting lymphatics in a rat model of metabolic syndrome

“…Fructose diet induction of MetSyn results in a twofold postprandial ApoB 48 chylomicron load (19,26), which positively associates with intestinal LPS uptake (32,63,72). High fructose diet feeding, in addition to high-fat diet feeding, increases gut permeability to dietary endotoxin (32,54).…”

“…High fructose diet feeding, in addition to high-fat diet feeding, increases gut permeability to dietary endotoxin (32,54). Dietary endotoxin readily associates with chylomicrons, which are primarily passed through the mesenteric lymphatics (66) along with many other gut peptides and hormones (44), suggesting that the primary trafficking of LPS is through lymphatic vessels (36,62,70,72). Lymphatic endothelial cells (42,52) and lymphatic muscle cells (unpublished observations) express multiple Toll-like receptors, are functionally responsive to LPS, and could potentially modulate their own inflam- matory activation (58).…”

Are Obesity-Related Insulin Resistance and Type 2 Diabetes Autoimmune Diseases?

“…This process may occur in nearby draining lymph nodes or mesenteric adipose tissue (106,107). Alternatively, gut antigens can be accessed by adaptive immune cells in local gut lymphoid structures, which can then leave the bowel and migrate to other tissues (92).…”

Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

“…Therefore, the mesenteric lymph could play an etiopathogenic role in the multiple organ dysfunction developed in the portal hypertensive syndrome [16]. Particularly, bacteria and toxins, like bacterial lipopolysaccharide (LPS), and inflammatory mediators with high affinity for chylomicrons, that is lipids, could use the mesenteric lymph vessels to bypass the liver and induce a systemic response [122].…”