A novel a/ß hydrolase domain protein derived from Haemonchus Contortus acts at the parasite-host interface

Authors: LU, MINGMIN - Nanjing Agricultural University; TIAN, XIAOWEI - Nanjing Agricultural University; TIAN, AI-LING - Nanjing Agricultural University; Li, Charles; YAN, RUOFENG - Nanjing Agricultural University; XU, LIXIN - Nanjing Agricultural University; SONG, XIAOKAI - Nanjing Agricultural University; LI, XIANGRUI - Nanjing Agricultural University

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/29/2020
Publication Date: 6/30/2020
Citation: Lu, M., Tian, X., Tian, A., Li, C.Z., Yan, R., Xu, L., Song, X., Li, X. 2020. A novel a/ß hydrolase domain protein derived from Haemonchus Contortus acts at the parasite-host interface. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2020.01388.
DOI: https://doi.org/10.3389/fimmu.2020.01388

Interpretive Summary: The a/ß-hydrolase domain (ABHD) proteins are ubiquitously distributed throughout all the organisms, and their functional roles have been implicated in energy metabolism, cell signalling, growth and development. In our previous work, we identified a novel ABHD protein derived from Haemonchus contortus excretory and 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 homologue with immune diagnostic utility and lipase activity. We further characterized the functional diversity of HcABHD as individual ES protein in parasite-host interactions. Moreover, recombinant HcABHD stimuli exerted critical controls on T cell cytokine production profiles. 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 to illuminate molecular and particularly immunomodulatory aspects of ES proteins and contribute to a better understanding of parasite immune evasion in H. contortus-host biology.

Technical Abstract: The a/ß-hydrolase domain (ABHD) proteins belonging to a/ß-hydrolase (ABH) superfamily are ubiquitously distributed throughout all the organisms, and their functional roles have been implicated in energy metabolism, cell signalling, growth and development. In our previous work, we identified a novel ABHD protein derived from Haemonchus contortus excretory and 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 homologue with immunodiagnostic utility and lipase activity. Given its catalytic activities and immunomodulatory potentials, we further investigated the functional diversity of HcABHD as 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 G0/G1 phase. Moreover, rHcABHD stimuli exerted critical controls on T cell cytokine production profiles, predominantly inhibiting the secretions of interleukin (IL)-4, interferon-gamma (IFN-') and transforming growth factor-beta (TGF-ß) 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 to illuminate molecular and particularly immunomodulatory aspects of ES proteins and contribute to a better understanding of parasite immune evasion in H. contortus-host biology. Key words: a/ß-hydrolase; H. contortus; excretory and secretory protein; immunomodulator; parasite-host interaction.