Proteomic analysis revealed T cell hyporesponsiveness induced by Haemonchus contortus excretory and secretory proteins

Authors: LU, MINGMIN - Nanjing Agricultural University; TIAN, XIAOWEI - Nanjing Agricultural University; YANG, ZHANG - Nanjing Agricultural University; WANG, WENJUAN - 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: Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/25/2020
Publication Date: 5/13/2020
Citation: Lu, M., Tian, X., Yang, Z., Wang, W., Tian, A., Li, C.Z., Yan, R., Xu, L., Song, X., Li, X. 2020. Proteomic analysis revealed T cell hyporesponsiveness induced by Haemonchus contortus excretory and secretory proteins. Veterinary Research. https://doi.org/10.1186/s13567-020-00790-0.
DOI: https://doi.org/10.1186/s13567-020-00790-0

Interpretive Summary: Gastrointestinal parasitic nematodes called Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to encourage the coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contributed to the regulation of host immune response so as to facilitate immune evasion and induce chronicity, but the responsible protein(s) and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 Haemonchus contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun LC-MS/MS protein analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could have diverse immune functions. Furthermore, the stimuli of HcESPs exerted critical controls on T cell cytokine production profiles. We predicted that these findings may contribute to gaining insights into the interaction between ES proteins and host key effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion, and providing new clues for novel vaccine development.

Technical Abstract: Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to encourage the coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contributed to the regulation of host immune response so as to facilitate immune evasion and induce chronicity, but the responsible protein(s) and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 Haemonchus contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun LC-MS/MS analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could inhibit T cell viability, induce Fas-engaged intrinsic and extrinsic apoptosis, suppress T cell proliferation and cause cell cycle arrest via limiting Akt/PKB signaling. Furthermore, the stimuli of HcESPs exerted critical controls on T cell cytokine production profiles, predominantly promoting the secretion of IL-10, IL-17A and TGF-ß1, and inhibiting IL-2, IL-4 and IFN-' production. Collectively, these findings may contribute to gaining insights into the interaction between ES proteins and host key effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion, and providing new clues for novel vaccine development. Keywords: Haemonchus contortus, excretory and secretory (ES) proteins, proteomic analysis, T cell, host-parasite interaction, immunomodulatory.