Tropomyosin: An Excretory/Secretory Protein from Haemonchus contortus Mediates the Immuno-Suppressive Potential of Goat Peripheral Blood Mononuclear Cells In Vitro

Abstract

During host-parasite interactions, binding of excretory/secretory proteins (ESPs) on the host immune cells is considered the fundamental phase for regulation of immune responses. In this study, gene encoding Haemonchus contortus tropomyosin (Hc-TpMy), was successfully cloned and expressed, and the recombinant protein after host cell surface attachment was evaluated for immune functional analysis with goat peripheral blood mononuclear cells (PBMCs) in vitro. The isopropyl-β-D-thiogalactopyranoside (IPTG)-induced recombinant protein was successfully recognized by the sera of rat experimentally infected with rHc-TpMy. The immunofluorescence assay detected attachment of rHc-TpMy on the surface of host PBMCs. Furthermore, immunoregulatory roles of rHc-TpMy on cytokines expression, PBMC proliferation, migration, nitric oxide (NO) production, apoptosis and monocytes phagocytosis were observed. The results showed that expression of IL-4 and IFN-γ cytokines, cell proliferation, NO production and PBMC migration were significantly suppressed by goat PBMCs after co-incubation with rHc-TpMy protein. However, the productions of IL-10, IL-17 and TGF-β1 cytokines, PBMCs apoptosis and monocytes phagocytosis were elevated at dose dependent manner. Our findings indicated that rHc-TpMy is an important ES binding protein exhibit distinct immuno-suppressive roles on goat PBMCs which might be a potential molecular target to control haemonchosis in future.

The GT1-TPS Structural Domain Protein From Haemonchus contortus Could Be Suppressive Antigen of Goat PBMCs

“…This indicated that Hc-TPS could be a suppressive antigen of goat PBMCs. Our results were consistent with previous studies ( 7 , 9 ). NOS catalyzes the creation of NO, citrulline from L-arginine, oxygen, and cofactors.…”

“…It was shown that H. contortus excretory/secretory products (HcESPs) coincubated with PBMCs in vitro inhibited the production of IL-4 and IFN-γ, suppressed cell proliferation and nitric oxide secretion, and promoted IL-10 secretion for anti-inflammatory effects ( 7 ). A variety of molecules derived from H. contortus nematodes have been identified to modulate the function of PBMCs, such as rHc-STP-1 ( 8 ) and rHc-TpMy ( 9 ), which have unique immunosuppressive effects on goat PBMCs and may be one of the mechanisms that promote immune evasion.…”

Calendula officinalis Triterpenoid Saponins Impact the Immune Recognition of Proteins in Parasitic Nematodes

“…GlcUAOA exposure led to dysfunctions in the cuticle layers; this may be associated with the action of tropomyosin, which plays a role in the catabolism of macromolecules in the cell wall during moulting. GlcUAOA also prevented protein recognition by hyperimmune rabbit serum and therefore the fact that GlcUAOA appears to reduce the potential of tropomyosin to suppress the host immune system [ 45 ] may offer promise in preventing parasite invasion. In addition, protective immunity may also be modulated by the galectin domain containing protein (GDC) present in larval stages [ 46 ].…”

Advances in the Development of Anti-Haemonchus contortus Vaccines: Challenges, Opportunities, and Perspectives

“…It was indicated that elongation factor 1 alpha (rHcEF-1α) played essential roles in the functional regulations of HcESPs on goat PBMCs by modulating IL-4, IL-17, IFN-γ, and TGF-β1 cytokine levels, in addition to some suppressive activities on host immune cells [ 92 ]. Apart from the discrete functional potency of different constituents of HcESPs on goat PBMCs, a recent research on tropomyocin protein showed the suppressive potential of rHc-TpMy on goat PBMCs by suppressing various immune functions of host PBMCs [ 93 ]. Recently, we have explored a novel immune modulator from HcESPs, which improved the IFN-γ, IL-4, and IL-2 cytokines production of host immune cells [ 94 ].…”