Mucosal immunity against parasitic gastrointestinal nematodes

Abstract

The last two decades witnessed significant advances in the efforts of immunoparasitologists to elucidate the nature and role of the host mucosal defence mechanisms against intestinal nematode parasites. Aided by recent advances in basic immunology and biotechnology with the concomitant development of well defined laboratory models of infection, immunoparasitologists have more precisely analyzed and defined the different immune effector mechanisms during the infection; resulting in great improvement in our current knowledge and understanding of protective immunity against gastrointestinal (GI) nematode parasites. Much of this current understanding comes from experimental studies in laboratory rodents, which have been used as models of livestock and human GI nematode infections. These rodent studies, which have concentrated on Heligmosomoides polygyrus, Nippostrongylus brasiliensis, Strongyloides ratti/S. venezuelensis, Trichinella spiralis and Trichuris muris infections in mice and rats, have helped in defining the types of T cell responses that regulate effector mechanisms and the effector mechanisms responsible for worm expulsion. In addition, these studies bear indications that traditionally accepted mechanisms of resistance such as eosinophilia and IgE responses may not play as important roles in protection as were previously conceived. In this review, we shall, from these rodent studies, attempt an overview of the mucosal and other effector responses against intestinal nematode parasites beginning with the indices of immune protection as a model of the protective immune responses that may occur in animals and man.

Fig. 1

A schematic representation of the interaction between GI nematode infections and under/malnutrition in the genesis of childhood anaemia and the effects on growth, cognitive ability and the ultimate decreased productivity in adulthood (Adapted and modified with permission from Guyatt, 2000).

Fig. 2

Antigen processing and presentation in the gut mucosa. Possible roles of Peyer's patch (PP) dendritic cells (DC) in the processing of luminal antigens which gain access to the PP across M cells located in the follicle-associated epithelium (FAE). Immature DC in the subepithelial dome, SED (1) acquire antigens, such as microbes via phagocytosis, and soluble antigens via pinocytosis. As these DC differentiate during movement to the interfollicular region (IFR), acquired antigens are processed and peptides are expressed in association with MHC class I and II antigens. In addition, adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and costimulatory molecules, such as B7-1 (CD80), B7-2 (CD86), and CD40, are upregulated, and the differentiation antigens M342 and NLDC-145 are expressed at high levels. In the IFR (2) they stimulate resident CD4⁺ and CD8⁺ T cells that have gained entry into the PP across high endothelial venules (HEV) located in the IFR, or these DC move into draining lymphatics, where they traffic to the mesenteric lymph nodes (MLN). A second possibility is that less differentiated DC in the SED process and present antigens to CD4⁺ T cells at this site (3) or after migration into the follicle (4), resulting in the induction of T cells with a phenotype that is unique to the PP, such as one producing transforming growth factor-β (TGF-β) and/or IL-10. In the follicule, such T cells would be ideally positioned to provide help for switching to IgA, a process that is then completed in the germinal centre. Following IgA switch and affinity maturation, B cells rapidly migrate from the PP to the MLN via efferent lymphatics, and finally to the lamina propria where they undergo terminal differentiation into plasma cells. It is however, not clear whether these possibilities are also applicable to the processing and presentation of nematode antigens in the gut mucosa (Adapted with permission from Kelsall and Strober, 1999).

Fig. 3

Schematic representation of IL-4 and IL-13 receptors. Anti-IL-4 mAb treatment blocks both IL-4 and IL-13 because both cytokines share (bind to) the type 2 IL-4R and activate STAT6 through this receptor. Thus, in the absence of IL-4, IL-13 is able to mediate worm expulsion via the IL-4Rα chain (Adapted and modified with permission from Finkelman et al., 1999).

Fig. 4

Daily faecal egg out (EPG) from wild type and FcRγ KO C57BL/6 mice infected subcutaneously with 3000 infective third stage larvae of S. venezuelensis. The figure 1 on the x-axis represents zero EPG.