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Differential gene expression at tick bite site

ABSTRACT: Alpha-gal syndrome (AGS) is a delayed allergic response to red meat caused by the production of alpha-gal-specific IgE following certain tick bites. We designed this study to characterize the underlying immune response to tick bites associated with AGS. Our results suggest that Amblyomma americanum bites direct mouse immunity toward Th2 following the initial burst of proinflammatory response and facilitate host sensitization to the α-gal antigen.

ORGANISM(S): Mus musculus

PROVIDER: GSE249650 | GEO | 2024/01/09

REPOSITORIES: GEO

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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:Background Human monocytotropic ehrlichiosis is an emerging life-threatening zoonosis caused by obligately intracellular bacterium, Ehrlichia chaffeensis. E. chaffeensis is transmitted by the lone star tick, Amblyomma americanum, and replicates in mononuclear phagocytes in mammalian hosts. Differences in the E. chaffeensis transcriptome in mammalian and arthropod hosts are unknown. Thus, we determined host-specific E. chaffeensis gene expression in human monocyte (THP-1) and in Amblyomma and Ixodes tick cell lines (AAE2 and ISE6) using a whole genome microarray. Methodology/Principal Findings The majority (~80%) of E. chaffeensis genes were expressed during infection in human and tick cells. There were few differences observed in E. chaffeensis gene expression between the vector Amblyomma and non-vector Ixodes tick cells, but extensive host-specific and differential gene expression profiles were detected between human and tick cells, including higher transcriptional activity in tick cells and identification of gene subsets that were differentially expressed in the two hosts. Differentially and host-specifically expressed ehrlichial genes encoded major immunoreactive tandem repeat proteins (TRP), the outer membrane protein (OMP-1) family, and hypothetical proteins that were 30–80 amino acids in length. Consistent with previous observations, high expression of p28 and OMP-1B genes was detected in human and tick cells, respectively. Notably, E. chaffeensis genes encoding TRP32 and TRP47 were highly upregulated in the human monocytes and expressed as proteins; however, although TRP transcripts were expressed in tick cells, the proteins were not detected in whole cell lysates demonstrating that TRP expression was post transcriptionally regulated. Conclusions/Significance Ehrlichia gene expression is highly active in tick cells, and differential gene expression among a wide variety of host-pathogen associated genes occurs. Furthermore, we demonstrate that genes associated with host-pathogen interactions are differentially expressed and regulated by post transcriptional mechanisms.

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Differential gene expression at tick bite site

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