Interactome analysis of CD5 and CD6 ectodomains with tegumental antigens from the helminth parasite Echinococcus granulosus sensu lato

Int J Biol Macromol. 2020 Dec 1:164:3718-3728. doi: 10.1016/j.ijbiomac.2020.08.219. Epub 2020 Sep 4.

Abstract

Echinococcus granulosus sensu lato (s.l.) is a cestode parasite affecting both human and livestock health. Recombinant ectodomains of human scavenger receptors CD5 (rshCD5) and CD6 (rshCD6) were previously reported to bind its tegumental antigens and to exert prophylactic effects in a murine model of infection. Although the properties of mammalian scavenger receptors include the binding to diverse pathogen-derived structures, their interaction with helminth parasites has been scarcely explored. Therefore, we report here a search for CD5 and CD6 interactors within E. granulosus s.l. antigens. Mass spectrometry analysis of pull-downs from soluble tegumental components with biotinylated rshCD5 and rshCD6 resulted in 17 and 11 overrepresented interactors, respectively, 8 of which were shared. The interactors included previously reported protective molecules against E. granulosus s.l. and/or other helminths. Similar studies performed with 11-mer peptides mapping to each of the three extracellular scavenger domains of CD5 and CD6 allowed an estimated molecular topology of the interactions. In conclusion, the fact that most helminth interactors identified for rshCD5 and rshCD6 were already reported as vaccine candidates or pharmacological targets against different helminthiases, supports the view that their beneficial effects in experimental infection results from binding to multiple relevant tegumental antigens.

Keywords: CD5; CD6; Echinococcus granulosus sensu lato; Interactome; Ligand; Scavenger receptor.

MeSH terms

  • Animals
  • Antigens, CD / genetics*
  • Antigens, Differentiation, T-Lymphocyte / genetics*
  • CD5 Antigens / genetics*
  • Echinococcosis / genetics
  • Echinococcosis / parasitology*
  • Echinococcus granulosus / genetics*
  • Echinococcus granulosus / pathogenicity
  • Genotype
  • Helminths / genetics
  • Helminths / parasitology
  • Humans
  • Mice
  • Protein Interaction Domains and Motifs / genetics

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD5 Antigens
  • CD6 antigen