Immunodulation and helminths: Towards new strategies for treatment of immune-mediated diseases?

Abstract

Parasitic helminths, and other persistent pathogens are able to produce molecules modulating the host immune response; hookworm for example produce the so-called neutrophil inhibitory factor (NIF), a protein which is the ligand of the integrin CD11b/CD18 present on the surface of neutrophil granulocytes, blocking the adherence of inflammatory cells to the endothelium. The cDNA for this protein derived from Ancylostoma caninum has been cloned and used in experimental models of neutrophil-mediated pathology, such as acute brain ischaemia, lung injury or experimental colitis and it was able to reduce tissue damage. For this reason, it has been postulated a possible therapeutic use of the protein in similar human conditions. Other molecules derived from helminths have been shown to interfere with host immune cells: it is the case of taeniaestatin from Taenia teniaeformis, of the 45 kDa glycoprotein from Trichinella spiralis or of the antigen B from Echinococcus granulosus, just to give few examples. The fact that most intestinal nematodes elicit a Th2 response in chronic infection has suggested the possibility to use experimental infections with such parasites for the treatment of Th1-mediated diseases, such as the inflammatory bowel diseases. Patients affected with Crohn's disease or ulcerative colitis were treated with the ova of a porcine whipworm Trichuris suis, which resulted in clinical amelioration of both diseases. The persistent Th2 activation occurring in nematode infection might represent an interesting model to evaluate the efficacy of factors able to activate Th1 responses: it is the case of the neutrophil activating protein from Helicobacter pylori, a toll-like receptor 2 agonist which has been shown to down-regulate eosinophilia and IgE synthesis in an experimental trichinellosis model. These results would suggest the possible use of this protein in the treatment of Th2-mediated disorders, such as allergic diseases. © Springer Science+Business Media B.V. 2010.