Unveiling the immunomodulatory properties of Haemonchus contortus adhesion regulating molecule 1 in the parasite-host interactions

Authors: LU, MINGMIN - Nanjing Agricultural University; TIAN, XIAOWEI - Nanjing Agricultural University; ZHANG, YANG - Nanjing Agricultural University; AIMULAJIANG, KALIBIXIATI - Nanjing Agricultural University; WANG, WENJUAN - Nanjing Agricultural University; EHSAN, MUHAMMAD - Nanjing Agricultural University; Li, Charles; YAN, RUOFENG - Nanjing Agricultural University; XU, LIXIN - Nanjing Agricultural University; LU, XIANGRUI - Nanjing Agricultural University

Submitted to: Parasites & Vectors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/21/2020
Publication Date: 8/18/2020
Citation: Lu, M., Tian, X., Zhang, Y., Aimulajiang, K., Wang, W., Ehsan, M., Li, C.Z., Yan, R., Xu, L., Lu, X. 2020. Unveiling the immunomodulatory properties of Haemonchus contortus adhesion regulating molecule 1 in the parasite-host interactions. Parasites & Vectors. https://doi.org/10.1186/s13071-020-04297-7.
DOI: https://doi.org/10.1186/s13071-020-04297-7

Interpretive Summary: Gastrointestinal nematodes could release excretory-secretory (ES) proteins into the host environment to ensure their survivals. These ES proteins act as immunomodulators to suppress or subvert 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. We hereby demonstrated that HcADRM1 with immunodiagnostic utility is a mammalian ADRM1 orthologs abundantly expressed at all developmental stages of H. contortus, and characterized the immunomodulatory property of HcADRM1 as an individual ES protein acting at the parasite-host interface. These findings may contribute to illumination of molecular and immunomodulatory characterization of ES proteins, as well as improvement of our understanding of parasite immune evasion in H. contortus-host biology.

Technical Abstract: Background: Gastrointestinal nematodes could release excretory-secretory (ES) proteins into the host environment to ensure their survivals. These ES proteins act as immunomodulators to suppress or subvert 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. Results: We hereby demonstrated that HcADRM1 with immunodiagnostic utility is a mammalian ADRM1 orthologs abundantly expressed at all developmental stages of H. contortus. Given the implications of ADRM1 in cell growth, survival and development, we next 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 arrested at G1 phase. Simultaneously, rHcADRM1 stimuli exerted critical controls on T cell cytokine secretion profiles, predominantly restraining the secretions of interleukin (IL)-4, IL-10 and interferon-gamma. Conclusions: Importantly, HcADRM1 protein may have therapeutic potential for anti-H.contortus vaccine development. Together, these findings may contribute to illumination of molecular and immunomodulatory characterization of ES proteins, as well as improvement of our understanding of parasite immune evasion in H. contortus-host biology. Key words: H. contortus; excretory and secretory protein; adhesion-regulating molecule 1 (ADRM1); immunomodulation; immune evasion