Abstract
The α/β-hydrolase domain (ABHD) proteins belonging to α/β-hydrolase (ABH) superfamily are ubiquitously distributed throughout all the organisms, and their functional roles have been implicated in energy metabolism, cell signaling, growth and development. In our preliminary work, we identified a novel ABHD protein derived from Haemonchus contortus excretory-secretory (ES) proteins (HcESPs) that interacted with host T cells. Here, we demonstrated that H. contortus ABHD (HcABHD) protein, expressed in all life-cycle stages of H. contortus, is a mammalian ABHD17 homolog with immunodiagnostic utility and lipase activity. Given its catalytic activities and immunomodulatory potentials, we further investigated the functional diversity of HcABHD as an individual ES protein in parasite-host interactions. HcABHD protein may serve as depalmitoylase or thioesterase to suppress cell viability, inhibit cell proliferation, induce intrinsic and extrinsic T cell apoptosis, and cause cell cycle arrested at G1 phase. Moreover, recombinant HcABHD stimuli exerted critical controls on T cell cytokine production profiles, predominantly by inhibiting the secretions of interleukin (IL)-4, interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) 1, and promoting IL-10 production. As the immunomodulator acting at the parasite-host interface, HcABHD protein may have potential applications for the vaccine development of therapeutic intervention. Together, these findings may help illuminate the molecular and particularly immunomodulatory aspects of ES proteins and contribute to an enhanced understanding of parasite immune evasion in H. contortus-host biology.
Highlights
The α/β-hydrolase domain (ABHD) proteins which are characterized with beta strands connected by alpha helices in common belong to α/β-hydrolase (ABH) superfamily including esterases, lipases, proteases, peroxidases, dehalogenases, and epoxide hydrolases [1]
A single band of ∼36 kDa was observed through the specific recognition of rHc-ABHD protein by anti-H. contortus serum (Figure 1B, Lane 3), whilst no band was recognized by normal goat serum (Figure 1B, Lane 4)
The native H. contortus ABHD (HcABHD) protein derived from Haemonchus contortus excretory-secretory (ES) proteins (HcESPs) was identified by rat anti-Recombinant HcABHD (rHcABHD) IgG as a single ∼34 kDa band (Figure 1B, Lane 5), whereas no positive bands were observed in the control groups (Figure 1B, Lane 6)
Summary
The α/β-hydrolase domain (ABHD) proteins which are characterized with beta strands connected by alpha helices in common belong to α/β-hydrolase (ABH) superfamily including esterases, lipases, proteases, peroxidases, dehalogenases, and epoxide hydrolases [1]. ABHD proteins are highly conserved and ubiquitously distributed throughout the organisms. Haemonchus contortus Abhydrolase Domain Protein mammalian ABHD family members with catalytic properties have been identified, and their physiological functions and biochemical substrates are still being elucidated [2]. Human ABHD2 was highly expressed in sperm and functioned as a lipid hydrolase through the activation of steroid hormone progesterone [3]. Human ABHD5, known as Chanarin-Dorfman syndrome protein, acted as a ligand-regulated lipase activator through the interaction with Perilipin to modulate lipolysis [5]
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