Helminth-host immunological interactions: prevention and control of immune-mediated diseases

Abstract

Exposure to commensal and pathogenic organisms strongly influences our immune system. Exposure to helminths was frequent before humans constructed their current highly hygienic environment. Today, in highly industrialized countries, contact between humans and helminths is rare. Congruent with the decline in helminth infections is an increase in the prevalence of autoimmune and inflammatory disease. It is possible that exclusion of helminths from the environment has permitted the emergence of immune-mediated disease. We review the protective effects of helminths on expression of inflammatory bowel disease, multiple sclerosis, and animal models of these and other inflammatory diseases. We also review the immune pathways altered by helminths that may afford protection from these illnesses. Helminth exposure tends to inhibit IFN-γ and IL-17 production, promote IL-4, IL-10, and TGF-β release, induce CD4(+) T cell Foxp3 expression, and generate regulatory macrophages, dendritic cells, and B cells. Helminths enable protective pathways that may vary by specific species and disease model. Helminths or their products likely have therapeutic potential to control or prevent immune-mediated illness.

Figure 1

Helminth-induced regulatory circuits that limit inflammation.

Figure 2

Male and female adult Heligmosomoides polygyrus bakeri. H. polygyrus bakeri is a nematode (round worm) that resides in the upper small intestine (duodenum and jejunum) of mice. The name of the parasite is changing from H. polygyrus to H. bakeri.

Figure 3

Helminth types successfully used to control immunological diseases. Helminths are divided into two phyla. The Nemathelminthes phylum contains the roundworms (Nematodes). The Platyhelminthes phylum contains the tapeworms (Cestodes) and the flukes (Trematodes). Although they are all called worms, the genetic distance between Nemathelminthes and Platyhelminthes is vast. The ability to parasitize another organism developed independently within these groups.