Cytokine regulation of resistance and susceptibility to intestinal nematode infection - from host to parasite

Abstract

Intestinal nematode infection is one of the most common forms of parasite infection worldwide. Both man and domestic stock suffer considerable morbidity from these infectious agents. The majority of our current understanding of the host parasite relationship to gut dwelling nematodes comes from well-defined laboratory models. One of the most informative over recent years has been study of whipworm infection in the mouse, Trichuris muris (T. muris). Infection in inbred strains of mouse shows a spectrum of response phenotypes reflecting the variation observed under natural conditions in the wild. Resistance and worm expulsion is mediated by CD4+ T helper two cells with a dominant role for interleukin (IL)-13. The effector mechanisms responsible for worm expulsion remain undefined but new evidence suggests a role for tumour necrosis factor alpha (TNF-alpha). Susceptibility to chronic infection is mediated through a T helper 1 (Th1) response characterised through the secretion of interferon gamma (IFN-gamma). A major new role for IL-18 has been defined in induction of a Th1 response through a novel down-regulation of IL-13. Moreover, progression to chronic infection may involve the parasite itself. T. muris secretes a protein that shares epitopes with host IFN-gamma, which may interfere with host protective cytokine, mediated protection and thus, promotes its own survival.