Immune Regulation by helminth parasites: cellular and molecular mechanisms

Helminths are multicellular worms that presently infect more than two billion humans worldwide. A large proportion of infections are clinically aysmptomatic, indicating that parasite-mediated downmodulation of immunity might reduce pathology.The typical features of the immune response to helminths are those of the T helper 2 (TH2) type — high levels of interleukin-4 (IL-4) and low levels of interferon-γ. However, the response might be more accurately described as a 'modified TH2-cell response', with high IL-10 and IgG4 antibody isotypes, and low IgE reactions.Studies in humans and experimental animal models indicate that regulatory T cells and suppressive macrophage populations might be important in downmodulating immune responses and pathology. We suggest that the regulatory environment results in the modified TH2-cell response.Molecular studies, involving both genomics and glycobiology, are identifying mediators from helminth parasites that are associated with immune regulation.One category of mediators are those that directly interfere with specific processes of immunity, for example a cysteine protease inhibitor that blocks MHC class II processing. Parasite cytokine homologues are also thought to be important.A second group of molecules are those, such as schistosome lipids, that interact with host dendritic cells to initiate a regulatory loop. So, helminths intervene from the first events in immune recognition to favour the development of a regulatory environment in which host and parasite can remain in a long-term homeostatic relationship.