A structurally distinct TGF-? mimic from an intestinal helminth parasite potently induces regulatory T cells.

ABSTRACT: Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-? signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-? mimic (Hp-TGM) that replicates the biological and functional properties of TGF-?, including binding to mammalian TGF-? receptors and inducing mouse and human Foxp3+ Treg cells. Hp-TGM has no homology with mammalian TGF-? or other members of the TGF-? family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host.

SUBMITTER: Johnston CJC 

PROVIDER: S-EPMC5701006 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature