Deciphering the genetic control of gene expression following Mycobacterium leprae antigen stimulation

Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong hostgenetic contribution to leprosy susceptibility is well established. However, the modulation ofthe transcriptional response to infection and the mechanism(s) of disease control are poorlyunderstood. To address this gap in knowledge of leprosy pathogenicity, we conducted agenome-wide search for expression quantitative trait loci (eQTL) that are associated withtranscript variation before and after stimulation with M. leprae sonicate in whole blood cells.We show that M. leprae antigen stimulation mainly triggered the upregulation of immunerelated genes and that a substantial proportion of the differential gene expression is geneticallycontrolled. Indeed, using stringent criteria, we identified 318 genes displaying ciseQTLat an FDR of 0.01, including 66 genes displaying response-eQTL (reQTL), i.e. ciseQTLthat showed significant evidence for interaction with the M. leprae stimulus. SuchreQTL correspond to regulatory variations that affect the interaction between human wholeblood cells and M. leprae sonicate and, thus, likely between the human host and M. lepraebacilli. [...