The Evolution and Diversity of Helminth Immunomodulation
(A) The TGF-β family is evolutionarily ancient, and nearly all helminth genomes (including free-living helminths) encode TGF-β family members. TGF-β homologs from Brugia malayi (Bm-TGH-2) and Fasciola hepatica (FhTLM) have co-evolved with their host to bind to the mammalian TGF-β receptor.
(B) In Heligmosomoides polygyrus, the CCP domain-containing family is over-represented in the genome, and HpTGM (a 5 CCP domain protein) has undergone convergent evolution to bind the TGF-β receptor, despite bearing no homology to the host cytokine. The CCP domain family in H. polygyrus appears highly adaptable, and the IL-33-blocking protein HpARI also consists of 3 CCP domains.
(C) T2 ribonucleases are involved in a number of homeostatic processes including RNA recycling, and most helminth genomes contain a member of this family. In the schistosomes, however, the T2 ribonuclease family has undergone expansion, and the T2 ribonucelase omega-1 (ω-1) is secreted into the host, where it gains entry to dendritic cells (DCs) through its Lewis X motifs which are bound by glycan receptors. Once inside the DC, omega-1 degrades host messenger and ribosomal RNA, suppressing DC activation and downstream T cell responses.
Blue arrows indicate evolutionary processes, black arrows indicate binding. Graphs show number of members of families in each group of genomes (WormBase ParaSite), represented as box and whiskers representing minimum to maximum values.