Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity.
Antje HäderSascha SchäubleJan GehlenNadja ThielemannBenedikt C BuerfentVitalia SchüllerTimo HessThomas WolfJulia SchröderMichael WeberKerstin HünnigerJürgen LöfflerSlavena VylkovaGianni PanagiotouJohannes SchumacherOliver KurzaiPublished in: Nature communications (2023)
Innate immune responses vary by pathogen and host genetics. We analyze quantitative trait loci (eQTLs) and transcriptomes of monocytes from 215 individuals stimulated by fungal, Gram-negative or Gram-positive bacterial pathogens. We identify conserved monocyte responses to bacterial pathogens and a distinct antifungal response. These include 745 response eQTLs (reQTLs) and corresponding genes with pathogen-specific effects, which we find first in samples of male donors and subsequently confirm for selected reQTLs in females. reQTLs affect predominantly upregulated genes that regulate immune response via e.g., NOD-like, C-type lectin, Toll-like and complement receptor-signaling pathways. Hence, reQTLs provide a functional explanation for individual differences in innate response patterns. Our identified reQTLs are also associated with cancer, autoimmunity, inflammatory and infectious diseases as shown by external genome-wide association studies. Thus, reQTLs help to explain interindividual variation in immune response to infection and provide candidate genes for variants associated with a range of diseases.
Keyphrases
- immune response
- gram negative
- multidrug resistant
- genome wide
- dendritic cells
- candida albicans
- genome wide association
- innate immune
- infectious diseases
- genetic diversity
- toll like receptor
- signaling pathway
- dna methylation
- young adults
- cell proliferation
- peripheral blood
- papillary thyroid
- copy number
- endothelial cells
- low density lipoprotein
- epithelial mesenchymal transition
- squamous cell carcinoma