Project description:Our object is to characterize the distinguish gene enrichment group in skin of Mycobacterium leprae (M. leprae)-infected footpads compared to that of Mycobacterium leprae (M. leprae) non-infected footpads.
Project description:Our object is to characterize the distinguish gene enrichment group in skin of Mycobacterium leprae (M. leprae)-infected footpads compared to that of Mycobacterium leprae (M. leprae) non-infected footpads. One-condition experiment, Skin of M. leprae non-infected footpads (control) vs. Skin of M. leprae infected footpads (sample). Biological replicates: 3 control and 3 sample, independently grown and harvested from isolator. One replicate per array.
Project description:Our goal is to understand the mechanism of granuloma formation in molecular level using Mycobacterium leprae (M. leprae)-infected footpads.
Project description:The initial interaction between a microbial pathogen and the host immune response influences the outcome of the battle between the host and the foreign invader. Leprosy, caused by the obligate intracellular pathogen Mycobacterium leprae, provides a model to study relevant human immune responses. Previous studies have adopted a targeted approach to investigate host response to M. leprae infection, focusing on the induction of specific molecules and pathways. By measuring the host transcriptome triggered by M. leprae infection of human macrophages, we were able to detect a host gene signature 24–48 hours after infection characterized by specific innate immune pathways involving the cell fate mechanisms autophagy and apoptosis. The top upstream regulator in the M. leprae-induced gene signature was NUPR1, which is found in the M. leprae-induced cell fate pathways. The induction of NUPR1 by M. leprae was dependent on the production of the type I interferon (IFN), IFN-β. Furthermore, NUPR1 mRNA and protein were upregulated in the skin lesions from patients with the multibacillary form of leprosy. Together, these data indicate that M. leprae induces a cell fate program which includes NUPR1 as part of the host response in the progressive form of leprosy
Project description:Our goal is to understand the mechanism of granuloma formation in molecular level using Mycobacterium leprae (M. leprae)-infected footpads. One-condition experiment, M. leprae non-infected footpads (control) vs. M. leprae infected footpads (sample). Biological replicates: 6 control, 6 (sample), independently grown and harvested from isolator. One replicate per array.
Project description:Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong host genetic contribution to leprosy susceptibility is well established. However, the modulation of the transcriptional response to infection and the mechanism(s) of disease control are poorly understood. To address this gap in knowledge of leprosy pathogenicity, we conducted a genome-wide search for expression quantitative trait loci (eQTL) that are associated with transcript 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 immune related genes and that a substantial proportion of the differential gene expression is genetically controlled. Indeed, using stringent criteria, we identified 318 genes displaying cis-eQTL at an FDR of 0.01, including 66 genes displaying response-eQTL (reQTL), i.e. cis-eQTL that showed significant evidence for interaction with the M. leprae stimulus. Such reQTL correspond to regulatory variations that affect the interaction between human whole blood cells and M. leprae sonicate, and thus likely between the human host and M. leprae bacilli. We found that reQTL are significantly enriched among binding sites of transcription factors that are activated in response to infection, and that they were enriched among single nucleotide polymorphisms (SNPs) associated with susceptibility to leprosy per se and Type-I Reaction, as well as SNPs targeted by recent positive selection. Our study suggests that natural selection shaped our genomic diversity to face pathogen exposure including M. leprae infection.
Project description:To this date, host transcriptome studies in leprosy have focused on Schwann cells, as well as mouse-footpad and skin biopsies. Despite macrophages being the most infected cell types in leprosy lesions, there is no genome-wide experiments with this model. Here, we aimed at identifying host macrophages transcriptional changes induced by live-Mycobacterium leprae infection for 48 hours.
