Research & Development
Parasitic helminths represent an extreme in the spectrum of pathogens, as large multicellular animals derived from free-living metazoan ancestors. Although commonly grouped together, the helminths in fact comprise two very distantly related taxa that diverged 600 million or more years ago, i.e., the roundworm nematodes and the flatworm plathelminths. Between these two main groups of distantly related helminth parasites, individual species of parasites have evolved to occupy a diverse range of niches within their hosts, using a wide range of infection strategies, yet with few exceptions the mammalian host responds to these diverse groups of organisms in a remarkably consistent and even stereotypical manner. Typically, this response involves the production of the cytokines interleukin-4 (IL-4), IL-5, IL-10, and IL-13, as well as immunoglobulin E (IgE) and the expansion and mobilization of specific effector cells, such as mast cells, eosinophils, and basophils. Collectively, this group of responses resembles the T-helper 2 (Th2) immune response. Th2 responses may serve the host by limiting the degree of helminthic organization.
Under experimental conditions, a number of helminths have been shown to induce Th2-type cytokine release and to downregulate the Th1 immune responses to unrelated bacterial and viral infections. Epidemiologic evidence, case control observations, animal studies and clinical studies all suggest that helminths may afford protection from or even treat autoimmune diseases. Therefore, colonization with intestinal helminths might be beneficial in reducing inflammation in patients with IBD, multiple sclerosis, and other autoimmune diseases.
An ideal biological agent should colonize the intestine without invading the host and should have little or no pathogenic potential. The source of the organism should be pathogen-free to minimize the potential of co-transmitting other diseases and it should not be a public health hazard to cohabitants or other close associates.
According to experiments performed thus far the porcine whipworm Trichuris suis seems to be an ideal candidate for development in IBD and other autoimmune diseases. T. suis is genetically related to Trichuris trichiura, the human whipworm, but it is not a human pathogen. In humans T. suis has no systemic phase, does not multiply in humans, is not directly transmittable by contact, and is cleared spontaneously. It has been shown experimentally that T. suis is able to colonize humans briefly without causing disease symptoms.