Influence of genetic variability on the immune response towards pathogens of systemic infections
Principal Investigator: Professor Oliver Kurzai
Approved Research ID: 57896
Approval date: June 24th 2020
Genetic variability has been shown to play a crucial role in the immune response. Blood monocytes are an important part of the innate immune response that cover a wide range of defense mechanisms including phagocytosis or release of cytokines against systemic fungal or bacterial infections. We aim to identify interindividual differences in the human immune response. Therefore we genotyped a healthy Caucasian male cohort (n = 230, age = 18-40, non-smoker, no medical treatments) to get the single-nucleotide-polymorphism (SNP) - profiles . Additionally, we generated transcriptome and cytokine release data for human monocytes derived from all donors after stimulation with A. fumigatus, N. meningitidis and S. aureus. We identified genome wide SNPs that influence the gene expression of stimulated monocytes (so called expression quantitative trait loci, eQTL) that allow the identification of genes whose expression is influenced by specific genotypes. Our study contributes to distinguish fungal from bacterial infection and bridges genetic variability and transcriptomic expression. Now we would like to compare our eQTL data with SNP profiles of specific patient cohorts from UK Biobank. Because we analyze the immune response towards pathogens of systemic infections, we aim a comparison with the UK Biobank Data for Septicaemia (A40 and A41). Within 6 month we aim to compare our data with SNP data from UK Biobank and expect to find overlaps. For these candidate SNPs, our eQTL study can provide the genes that are influenced by them. This work has a public health impact because it provides new insights in interindividual differences in the immune response and can be used to identify causal genes for candidate SNPs that are associated with a disease. To understand the mechanisms how SNPs influence the immune response is the basis to develop new personalized therapeutic approaches.