Project description:This study provides a multi-omics approach to determine the effect on the transcriptome and proteome gut profiles of zebrafish inoculated with tick saliva followed by mammalian meat consumption. With bioinformatics analysis using the R software, we sought for significant biological and metabolic pathway changes, in order to fill up some of the current knowledge gaps associated with the alpha-Gal syndrome (AGS). In addition, ortholog mapping allowed to obtain highly concordant biological 1:1 human ortholog genes for the detection of gene-disease associations (GDAs) and disease enriched pathways. Further data validation was performed using reverse transcriptase quantitative PCR (RT-qPCR) and Western Blot (WB) analysis on target differentially expressed genes (DEGs) and differentially represented proteins (DRPs), respectively. We found that treatment with tick saliva increased mortality and caused significant higher incidence of hemorrhagic type allergic reactions, changes in behavior and feeding patterns. Transcriptomics analysis showed downregulation of biological and metabolic pathways correlated with anti-Gal IgE and allergic reactions to tick saliva such as blood circulation, cardiac and vascular smooth muscle contraction, behavior and sensory perception. Disease enrichment analysis revealed that downregulated orthologous genes were mostly associated with human disorders affecting the nervous, musculoskeletal, and cardiovascular systems. Proteomics analysis predominantly revealed suppression of biological and metabolic pathways associated with the immune system production of reactive oxygen species (ROS) and cardiac muscle contraction. The underrepresented proteins were mainly linked to nervous and nutritional/metabolic human disorders. Furthermore, 12 DEGs were found to have concomitant protein-level representation. Lastly, the integration of transcriptomics and proteomics layers through multi-omics pathway enrichment revealed inhibition of pathways associated with adrenergic signaling in cardiomyocytes, as well as heart and muscle contraction. This research contributed to the discovery of AGS-related biological pathways, reinforcing disease multisystemic organ involvement and linking α-Gal sensitization with other illnesses. Furthermore, our results shed light on novel bioinformatic strategies for the identification of key genes and proteins that may serve as potential disease biomarkers.

Project description:Inducing the long-term protection via effector memory CD8+ T cells residing in the peripheral tissues is the ultimate goal of T cell-based vaccination strategies. CD8+ T cell reacting against a particular set of antigenic peptides show propensity to generate stable pools of memory inflating cells with profound protective capacity. While the epitopes that induce memory inflation have been thoroughly characterized and used as excellent constituents of vaccines such as recombinant adenoviruses, the identity of the tissue factors responsible for maintaining memory inflating CD8+ T cells remains elusive. Here, we have used a Cre recombinase-dependent, -galactosidase (gal)–recombinant adenovirus vector that allowed for cell-specific expression of gal epitopes and identification of cell types involved in generation of inflationary responses. While targeting antigen expression to classical hematopoietic antigen presenting cells was insufficient to activate gal-specific CD8+ T cells, expressing the antigen exclusively in CCL19-producing fibroblastic stromal cells (FSCs) induced robust anti-gal CD8+ T cell response. Using bone marrow chimera mice to abolish the expression of major histocompatibility complex I (MHC-I) and Basic Leucine Zipper ATF-Like Transcription Factor 3 (BATF3) in hematopoietic cells we demonstrated that CCL19-expressing FCS function as antigen libraries, gradually releasing the antigen to CD103+ DCs to maintain gal-specific memory inflating population. Moreover, targeted ablation of CCL19-producing cells revealed that pulmonary fibroblastic stromal cells act as the principal organizer of the nurturing niches that support the metabolic conversion in CD8+ T cells necessary for the generation of long-lasting protective inflationary responses. Overall, our data reveal a hitherto unknown function of CCL19-expressiong fibroblastic stromal in supporting the metabolic fitness of CD8+ T cells, thereby promoting the generation of tissue-specific and long-lasting protective CD8+ T cell responses.

Dataset Information

Transcriptomics insights into the functional role of tick Ixodes ricinus midgut proteins metalloprotease and antigen p23

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets