title: Global gene transcriptome analysis in vaccinated cattle revealed a dominant role of IL-22 for protection against bovine tuberculosis.
abstract: Bovine tuberculosis (bTB) is a chronic disease of cattle caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex group of bacteria. Vaccination of cattle might offer a long-term solution for controlling the disease and priority has been given to the development of a cattle vaccine against bTB. Identification of biomarkers in tuberculosis research remains elusive and the goal is to identify host correlates of protection. We hypothesized that by studying global gene expression we could identify in vitro predictors of protection that could help to facilitate vaccine development. Calves were vaccinated with BCG or with a heterologous BCG prime adenovirally vectored subunit boosting protocol. Protective efficacy was determined after M. bovis challenge. RNA was prepared from PPD-stimulated PBMC prepared from vaccinated-protected, vaccinated-unprotected and unvaccinated control cattle prior to M. bovis challenge and global gene expression determined by RNA-seq. 668 genes were differentially expressed in vaccinated-protected cattle compared with vaccinated-unprotected and unvaccinated control cattle. Cytokine-cytokine receptor interaction was the most significant pathway related to this dataset with IL-22 expression identified as the dominant surrogate of protection besides INF-γ. Finally, the expression of these candidate genes identified by RNA-seq was evaluated by RT-qPCR in an independent set of PBMC samples from BCG vaccinated and unvaccinated calves. This experiment confirmed the importance of IL-22 as predictor of vaccine efficacy.
authors.affiliation: Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Sabin
authors.initials: S
authors.lastname: Bhuju
authors.forename: Elihu
authors.initials: E
authors.lastname: Aranday-Cortes
authors.forename: Bernardo
authors.initials: B
authors.lastname: Villarreal-Ramos
authors.forename: Zhou
authors.initials: Z
authors.lastname: Xing
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.forename: H Martin
authors.initials: HM
authors.lastname: Vordermeier
mesh_terms: D000818:Animals; D002417:Cattle; D054405:Chemokine CCL3 / Q000276:immunology; D020869:Gene Expression Profiling; D007371:Interferon-gamma / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D053513:Matrix Metalloproteinase 16 / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology*; D017423:Sequence Analysis, RNA; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D014380:Tuberculosis, Bovine / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination; D000097043:Interleukin-22
chemical_list: D054405:Chemokine CCL3; D007371:Interferon-gamma; D018793:Interleukin-13; D007378:Interleukins; D053513:Matrix Metalloproteinase 16; D032581:Tuberculosis Vaccines; D000097043:Interleukin-22