Helminths and intestinal barrier function

Abstract

Approximately one-sixth of the worlds' population is infected with helminths and this class of parasite takes a major toll on domestic livestock. The majority of species of parasitic helminth that infect mammals live in the gut (the only niche for tapeworms) where they contact the hosts' epithelial cells. Here, the helminth-intestinal epithelial interface is reviewed in terms of the impact on, and regulation of epithelial barrier function, both intrinsic (epithelial permeability) and extrinsic (mucin, bacterial peptides, commensal bacteria) elements of the barrier. The data available on direct effects of helminths on epithelial permeability are scant, fragmentary and pales in comparison with knowledge of mobilization of immune reactions and effector cells in response to helminth parasites and how these impact intestinal barrier function. The interaction of helminth-host and helminth-host-bacteria is an important determinant of gut form and function and precisely defining these interactions will radically alter our understanding of normal gut physiology and pathophysiological reactions, revealing new approaches to infection with parasitic helminths, bacterial pathogens and idiopathic auto-inflammatory disease.

Keywords: cestode; enteric microbiota; mucin; nematode; parasitic worm.

Figure 1.

Panel A provides a simplified phylogenic overview of parasitic helminths with typical examples of species that infect humans or are common in laboratory studies (definitive host in parentheses). Detailed classification can be found in “Introduction to Animal Parasitology” by J.D. Smyth, Cambridge University Press, 1994: Anasakis simplex, Ancylostoma duodenale, Ascaris lumbricoides, Ascaris suum, Brugia malayi, Diphyllobothrium latum, Clonorchis sinensis, Dracunculus medinensis, Echinococcus granulosus, Enterobius vermicularis, Heligmosomoides polygyrus, Hymenolepis diminuta, Necator americanus, Nippostrongylus brasiliensis, Schistosoma mansoni, Strongyloides stercorlis, Strongyloides ratti, Taenia saginata, Taenia solium, Toxocara canis, Trichinella spiralis, Trichuris trichiura, Trichuris muris, Trichuris suis, Wuchereria bancrofti). In Panel B the generic complexity of the lifecycle of parasitic helminths is shown along with an inset box presenting essential features of successful parasites (synchronization of the parasite life-cycle with host reproductive cycle is not critical but could be advantageous).

Figure 2.

Schema showing the variety of possible mechanisms by which T cell activation following helminth infection could affect epithelial permeability and intestinal barrier function (E/S, helminth-derived excretory/secretory products; IL, interleukin; TGF, transforming growth factor; Th2, T-helper cell type-2; T_reg, regulatory T cells).

Figure 3.

Schematic overview of the mechanisms by which infection with intestinal parasitic helminths (worm or their excretory/secretory products (ESP)) can directly or indirectly impact the barrier function of the gut (IL, interleukin; MLN, mesenteric lymph nodes; TH2, T-helper cells type 2; TSLP, thymic stromal lymphopoietin).