Abstract
BackgroundGastrointestinal 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.MethodsBased 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.ResultsWe 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.ConclusionsImportantly, 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.
Highlights
Gastrointestinal nematodes could release excretory-secretory (ES) proteins into the host environment to ensure their survival
In a previous study [15], we identified 114 Haemonchus contortus excretory-secretory (ES) proteins (HcESPs) that interacted with host T cells via liquid chromatography mass spectrometry (LC-MS/MS) analysis
A single band ~ 46 kDa was observed through the specific recognition of rHcADRM1 protein by antiH. contortus serum (Fig. 1c; Lane 2), while no band was identified via healthy goat sera (Fig. 1c; Lane 3)
Summary
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. With engagement in the Ub proteasome pathway that regulates a broad range of physiological functions, ADRM1 is implicated in multitudinous cellular processes such as cell growth, migration, survival and development, in cancer cells [8]. Fejzo et al [12] demonstrated that overexpression of ADRM1 in ovarian cancer promoted cell growth and migration, whereas blocking its expression caused cell death. Comparable expressions of ADRM1 have been observed in several lymphocyte cell lines as well as endothelial cell lines, and similar physiological roles of ADRM1 are described through its excessive expression in skin endothelial cells that facilitates T lymphocyte adhesion [14]
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