Increased Intestinal Endotoxin Absorption During Enteric Nematode but Not Protozoal Infections Through a Mast Cell-Mediated Mechanism

Abstract

It is known that hypersensitivity reactions in the gastrointestinal tract, which are primarily mediated by mast cells, are associated with a secretory response of the epithelium and often increased permeability to macromolecules. Studies to date have not examined the effects of hyperpermeability on the absorption of toxic substances normally present in the intestinal lumen such as bacterial LPS. In the present study, we observed that Strongyloides venezuelensis infection in mice decreases the mRNA expression of intestinal epithelial cell junctional molecules (occludin and zonula occludens 1) and increases portal endotoxin levels 4 h after intragastric administration of LPS (20 mg/kg body weight). Furthermore, an increase in the flux of immunoglobulin G into the intestinal lumen was observed 10 days postinfection (PI). An increased rate of LPS absorption was also seen in mice infected with Nippostrongylus brasiliensis on day 14 PI and rats concurrently infected with S. venezuelensis and N. brasiliensis on day 20 PI. On the other hand, infection with Eimeria vermiformis and Eimeria pragensis was not observed to enhance LPS absorption 4 h after intragastric administration of LPS (20 mg/kg body weight), although E. vermiformis infection did inhibit the epithelial cell mRNA expression of zonula occludens 1, but not occludin, on day 9 PI, resulting in a reduced immunoglobulin G flux than that produced by S. venezuelensis infection. Our results suggest that mastocytosis accompanying intestinal nematode infection increases the intestinal absorption of LPS into the portal circulation by suppressing the expression of tight junction molecules.

Duodenal Helminth Infection Alters Barrier Function of the Colonic Epithelium via Adaptive Immune Activation

“…3) analysis provide evidence to suggest that H. polygyrus infection also induces alterations in the paracellular pathway, suggesting the impact of helminth infection on both paracellular and transcellular pathways, contributing to increased epithelial permeability. These observations are supported by the results showing that intestinal helminth infection increases the intestinal translocation/ absorption of bacterial products such as lipopolysaccharide (LPS) into the portal circulation by altering barrier function (10) and that IL-4 treatment of keratinocytes significantly enhanced the permeability to high-molecular-mass material (40-kDa fluorescein isothiocyanate [FITC]-dextrans) through modification of intercellular adhesion molecules (23). In contrast, a recent study that used an Ussing chamber approach measured mucosal permeability and secretion ex vivo and showed that H. polygyrus infection increased colonic mucosal resistance (34).…”

Microbial Translocation Associated with an Acute-Phase Response and Elevations in MMP-1, HO-1, and Proinflammatory Cytokines in Strongyloides stercoralis Infection

“…Previous reports have shown that infection with intestinal helminths is characterized by an enhanced leakiness of the intestinal epithelium, mediated by activated mast cells, which can lead to the movement of bacterial LPS into the portal circulation (10,11). Studies using experimental animal models suggest that intestinal injury and systemic endotoxemia are two major factors leading to morbidity in helminth infections (11,18).…”

“…Studies using experimental animal models suggest that intestinal injury and systemic endotoxemia are two major factors leading to morbidity in helminth infections (11,18). Infection with the enteric nematodes Trichinella spiralis and Strongyloides venezuelensis has been shown to be associated with an enhanced leakiness of the intestinal epithelium and the translocation of LPS into the circulation (10,11). Even in nonintestinal helminth infections, such as infections by schistosomes that reside in the mesenteric veins, damage caused by worm eggs traversing the gastrointestinal epithelium can result in the systemic translocation of bacteria (18,19).…”

“…Although bacterial translocation is known to occur in infections affecting the integrity of the gut epithelium (10,11), very few studies have examined the occurrence of this phenomenon in intestinal helminth infections. Among the common helminth parasites known to establish chronic infections in humans, Strongyloides stercoralis, the causative agent of strongyloidiasis (12), is unique in its ability to exist in free-living and autoinfective cycles (13,14), with the latter allowing persistent long-lived infection.…”

IgE and mast cells in host defense against parasites and venoms

“…mMCP1 released by MCs upon T. spiralis infection can potentially degrade occludin and other tight junction proteins, compromising intestinal barrier function and thereby promoting intestinal inflammation and pathology [82]. Based on studies in C57BL/6J WT mice, it has been proposed that MCs may contribute to the epithelial hyper-permeability associated with reductions in tight junction proteins (occludin and zonula occludens 1) that is observed after infection with either S. venezuelensis or N. brasiliensis , and that this may enhance both systemic absorption of endotoxin through the gut and IgG flux into intestine lumen [122]. …”