Unveiling the immunomodulatory properties of Haemonchus contortus adhesion regulating molecule 1 interacting with goat T cells

Abstract

Background Gastrointestinal nematodes could release excretory-secretory (ES) proteins into the host environment to ensure their survival. These ES proteins act as immunomodulators to suppress or subvert the host immune response via the impairment of immune cell functions, especially in chronic infections. In our preliminary study, Haemonchus contortus adhesion-regulating molecule 1 (HcADRM1) was identified from H. contortus ES proteins (HcESPs) that interacted with host T cells via liquid chromatography-tandem mass spectrometry analysis. However, little is known about HcADRM1 as an ES protein which may play a pivotal role at the parasite-host interface. Methods Based on bioinformatics approaches, multiple amino acid sequence alignment was conducted and the evolutionary relationship of HcADRM1 with ADRM1 orthologues was extrapolated. Employing RT-qPCR and immunohistochemistry assays, temporal transcriptional and spatial expression profiles of HcADRM1 were investigated. Using immunostaining approaches integrated with immunological bioassays, the immunomodulatory potentials of HcADRM1 on goat T cells were assessed. Results We hereby demonstrated that HcADRM1 with immunodiagnostic utility was a mammalian ADRM1 orthologue abundantly expressed at all developmental stages of H. contortus . Given the implications of ADRM1 proteins in cell growth, survival and development, we further investigated the immunomodulatory property of HcADRM1 as an individual ES protein acting at the parasite-host interface. The rHcADRM1 stimuli notably suppressed T cell viability, promoted intrinsic and extrinsic T cell apoptosis, inhibited T cell proliferation and induced cell cycle arrest at G1 phase. Simultaneously, rHcADRM1 stimuli exerted critical controls on T cell cytokine secretion profiles, predominantly by restraining the secretions of interleukin (IL)-4, IL-10 and interferon-gamma. Conclusions Importantly, HcADRM1 protein may have prophylactic potential for anti- H. contortus vaccine development. Together, these findings may contribute to the clarification of molecular and immunomodulatory traits of ES proteins, as well as improvement of our understanding of parasite immune evasion mechanism in H. contortus -host biology.

The excretory–secretory antigen HcADRM1 to generate protective immunity against Haemonchus contortus

“…Hence, anti-rHcADRM1 IgG was employed in the parallel passive trial and was shown to confer encouraging levels of protection to inoculated goats by reducing cumulative FEC and worm burden by 46.7 and 56.2%, respectively. In this study, relatively high levels of mucosal and serum anti-rHcADRM1 IgG were present in HcADRM1 preparations-immunized goats over the time-courses of both trials 1 and 2, which might impede H. contortus larvae development given the crucial roles of HcADRM1 protein in transcriptional regulation and cell growth (Lu et al, 2020c). In most cases, immunization with native antigen preparations appears to induce higher levels of protective immune responses against H. contortus compared to the corresponding recombinant or synthetic forms.…”

“…2E and F). Given that the preliminary work identified higher HcADRM1 mRNA expression in male worms of H. contortus than in female ones (Lu et al, 2020c), we anticipated the administration of HcADRM1 preparations would show a significant protection pattern against male adults. However, similar to trial 1, no notable changes in either female or male worm burdens (P = 0.051 and P = 0.161, respectively) were observed between groups E and F (Fig.…”

“…The production of control goat pAbs or HcADRM1-specific pAbs was carried out as previously described (Lu et al, 2020c). In the primary immunization, goats (n = 3) were administered subcutaneously with rHcADRM1 protein (300 μg) or PBS blended with the equivalent volume of complete Freund's adjuvant (CFA; Sigma-Aldrich).…”

“…In our preliminary study, H. contortus ADRM1 (HcADRM1) protein was identified from ES antigens that impaired T-cell functions by immunoproteomic approaches combined with immunological bioassays (Lu et al, 2020b). Besides, HcADRM1 protein expressed throughout H. contortus life cycle was then demonstrated to act as an immunomodulator that interfered with numerous host cellular events in vitro, including T-cell viability, proliferation, apoptosis, signalling and cytokine production (Lu et al, 2020c). Given the prophylactic potential of HcADRM1 protein, we hereby validated immune protective efficacies of HcADRM1 preparations in protecting goats against H. contortus challenge.…”

Haemonchosis in Sheep and Goats, Control Strategies and Development of Vaccines against Haemonchus contortus

“…Another ES antigen, adhesion-regulating molecule 1 (HcADRM1), was expressed in E. coli in its soluble form and tested in goats. Results indicated that vaccination with recombinant HcADRM1 induced a slightly protective immunity in comparison to rHcABHD, with reductions of 48.9% in FECs and up to 58.6% in worm burdens [ 68 , 96 ].…”