Regulation of the immune system in metazoan parasite infections.

Eukaryotic, multicellular parasites such as the helminth worms have a major impact on the mammalian immune system in two contexts. First, they have evolved sophisticated strategies for long-term immune evasion including recruiting natural suppressive mechanisms such as the regulatory T cell (Tregs). Tregs play a role not only in repressing immunity to parasites, but also in dampening bystander responses such as those to allergens. To achieve these effects, they produce a range of immunomodulators some of which are evolutionary homologues of immune system cytokines, while others are novel proteins capable of interfering with immune cell signalling and differentiation. The second context in which metazoa may have influenced their host is at the level of genetic polymorphism in immune response genes. Alleles at loci originally associated with predisposition to asthma have more recently been found to confer heightened resistance to helminth parasites. This may suggest a mechanistic link between more vigorous type 2 responses in both allergy and infection. On a broader perspective, one may speculate that alleles advantageous in the historical environment of prevalent infection, now display a deleterious phenotype in our more 'hygienic' societies.