Transcriptional and proteomic analysis reveal recombinant galectins of Haemonchus contortus down-regulated functions of goat PBMC and modulation of several signaling cascades in vitro

Abstract

In this study, a combined proteomic and transcriptomic analysis was performed to understand the mechanisms underlying the immunomodulation induced by recombinant galectins of Haemonchus contortus (rHco-gal-m/f) on goat peripheral blood mononuclear cells (PBMC). We demonstrated that rHco-gal-m/f could be distinguished by antisera from goats experimentally infected with H. contortus and bound to the surface of goat PBMC. Following rHco-gal-m/f exposure, 16 differentially expressed proteins were identified, which function in biological processes such as stimulus response, biological regulation and localization. According to Gene Ontology Annotation, 15 proteins (93.8%) had binding activity and 9 proteins (56.3%) had catalytic activity. A series of transcriptomic analyses were performed subsequently to assess the expression change of certain pathway members. The integrated results of proteomic and transcriptomic analysis suggested that the activation of VEGF pathway, free radical producing pathway, NFκB pathway and ubiquitin-proteasome pathway was inhibited following exposure to rHco-gal-m/f, while the TLR pathway and CASPASE pathway were activated. Cytokine production and T cell differentiation were also influenced. Cell migration assays and ELISA were performed and the results were in accordance with the change of the proteins and genes. The protein and gene profiles determined here identified several mechanisms underlying the rHco-gal-m/f-induced immunomodulation of goat PBMC. This research provided insight into the interactive relationship between parasitic nematode galectins and host PBMC. It also shed new lights on the understanding of molecular mechanisms of helminthic immune evasion.