Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

Parasit Vectors. 2020 Sep 7;13(1):454. doi: 10.1186/s13071-020-04333-6.

Abstract

Background: Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo.

Methods: In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion.

Results: We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD downregulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression.

Conclusions: These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

Keywords: Haemonchus contortus; Immunomodulation; Peripheral blood mononuclear cell (PBMC); Rhodanese.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cloning, Molecular
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Goat Diseases / immunology*
  • Goat Diseases / parasitology
  • Goat Diseases / therapy
  • Goats / immunology
  • Goats / parasitology
  • Haemonchiasis / immunology
  • Haemonchiasis / therapy
  • Haemonchiasis / veterinary
  • Haemonchus / immunology*
  • Haemonchus / metabolism
  • Helminth Proteins / biosynthesis
  • Helminth Proteins / immunology
  • Host-Parasite Interactions
  • Immunomodulation* / drug effects
  • Immunomodulation* / physiology
  • Major Histocompatibility Complex / drug effects
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / metabolism
  • Phagocytosis / drug effects
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / pharmacology
  • Thiosulfate Sulfurtransferase* / biosynthesis
  • Thiosulfate Sulfurtransferase* / pharmacology

Substances

  • Cytokines
  • Helminth Proteins
  • Recombinant Proteins
  • Thiosulfate Sulfurtransferase