MiRNA expression profile in leprosy skin biopsy specimens
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Philip Liu
PROVIDER: E-GEOD-33192 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Skin biopsy specimens of skin lesions were profiled for miRNA expression. In this study, we indentified miRNA species that were differentially expressed in the skin lesions of either the lepromatous or tuberculoid forms of leprosy. One miRNA species, hsa-mir-21, found in the lepromatous lesions was capable of downregulating the vitamin D-dependent antimicrobial pathway.
2011-12-31 | GSE33192 | GEO
Project description:Neutrophil recruitment is pivotal to host defense against microbial infection, but also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy (L-lep), and is characterized by neutrophil infiltration in lesions, the most overrepresented biologic functional group was “cell movement” including E-selectin, which was coordinately regulated with IL-1. In vitro activation of TLR2, upregulated in ENL lesions, triggered induction of IL-1, which together with IFN-, induced E-selectin expression on, and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2/FcR activation, neutrophil migration and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease. 6 ENL skin lesions and 7 Lepromatous leprosy skin lesions
2009-06-30 | E-GEOD-16844 | biostudies-arrayexpress
Project description:Granulomas are complex cellular structures comprised predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated single cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RR), a dynamic process in which some patients with disseminated lepromatous leprosy (L-lep) transition towards self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions, and regulated by IFN- and IL-1. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts contribute to the antimicrobial response.
2021-05-04 | GSE167889 | GEO
Project description:Transcriptome profiles derived from the site of human disease has led to the identification of genes that contribute to pathogenesis, yet the complex mixture of cell types in these lesions has been an obstacle for defining specific mechanisms. Leprosy provides an outstanding model to study host defense and pathogenesis in a human infectious disease, given its clinical spectrum which interrelates with the host immunologic and pathologic responses. Here, we investigated gene expression profiles derived from skin lesions for each clinical subtype of leprosy, analyzing gene co-expression modules by cell type deconvolution. In lesions from tuberculoid leprosy patients, those with the self-limited form of the disease, dendritic cells were linked with MMP12 as part of a tissue remodeling network that contributes to granuloma formation. In lesions from lepromatous leprosy patients, those with disseminated disease, macrophages were linked with a gene network that programs phagocytosis. In erythema nodosum leprosum, neutrophil and endothelial cell gene networks were identified as part of the vasculitis that results in tissue injury. The present integrated computational approach provides a systems approach towards identifying cell-defined functional networks that contribute to host defense and immunopathology at the site of human infectious disease.
2016-08-30 | GSE84893 | GEO
Project description:Neutrophil recruitment is pivotal to host defense against microbial infection, but also contributes to the immunopathology of disease. We investigated the mechanism of neutrophil recruitment in human infectious disease by bioinformatic pathways analysis of the gene expression profiles in the skin lesions of leprosy. In erythema nodosum leprosum (ENL), which occurs in patients with lepromatous leprosy (L-lep), and is characterized by neutrophil infiltration in lesions, the most overrepresented biologic functional group was 'cell movement' including E-selectin, which was coordinately regulated with IL-1beta. In vitro activation of TLR2, upregulated in ENL lesions, triggered induction of IL-1beta, which together with IFN-gamma, induced E-selectin expression on, and neutrophil adhesion to endothelial cells. Thalidomide, an effective treatment for ENL, inhibited this neutrophil recruitment pathway. The gene expression profile of ENL lesions comprised an integrated pathway of TLR2/FcR activation, neutrophil migration and inflammation, providing insight into mechanisms of neutrophil recruitment in human infectious disease.
2009-06-30 | GSE16844 | GEO
Project description:[Aim] To characterize the transcriptomic changes in skin lesions of lepromatous leprosy patients before and after multidrug therapy (MDT). Likewise, not all patients improve their bacillary index after MDT. Thus, the further analysis aims to compare patients who responded or did not to MDT and identify underlying modulated genes. [Design] Lepromatous patients were treated for 12 months with multidrug therapy. Skin biopsy samples were collected before (BT) and after treatment (AT). At the end of 12 months of MDT, those who decreased their bacillary index by at least one log10 unit were considered responders (R) and otherwise non-responders (NR). RNA was isolated, poly-A captured, and sequenced. Comparisons both within-patient and between-patients were done. [Results] At the end of MDT, genes involved with lipid metabolism, innate and adaptive immunity, extracellular matrix, and epidermis development were all differentially expressed. Comparisons between responders and non-responders to MDT identified differentially expressed genes involved with lipid metabolism, semaphorin-plexin signaling pathway, epidermis development, and vasculogenesis. This study identified gene expression signatures modulated after 12 months of MDT. Also, a subset of patients with poor bacterial clearance has dysregulated pathways relative to responders.
2022-04-10 | E-MTAB-11605 | biostudies-arrayexpress
Project description:Here we report the data generated by short-read sequencing of mRNA (polyA) isolated from granuloma annulare and leprosy skin lesions. Our main aim was to identify putative mRNA biomarkers for distinguishing leprosy from other differential diagnoses. Additionally, we also explored the distinction between MB and PB by using differential expression analysis as well as training a penalized logistic regression to select important features. Our results showed that few genes are enough to differentiate leprosy lesions, including paucibacillary cases, from other morphological and histopathological similar skin diseases. Some of these genes have been replicated in a larger and more heterogeneous sample with RT-qPCR, validating their classification potential. We also suggest important novel gene candidates to improve our understanding of molecular differences between MB and PB lesions, which could either pinpoint new pathways and targets for host-based specialized adjuvant treatment for leprosy. Finally, this dataset has been used to explore the relationship between cornification and keratinocyte-related genes and TGFB-mediated epithelial-mesenchymal transition (EMT), which could indicate that in skin, M. leprae could be de-differentiating, directly or indirectly, other cell types into a progenitor/stem-like phenotype, facilitating mycobacterial survival and migration within the host. Alternatively, this could highlight which pathways are activated during granuloma formation and/or skin barrier assembly/disassembly.
2021-10-01 | E-MTAB-10318 | biostudies-arrayexpress
Project description:Comparison of spatial sequencing in leprosy lesions from lepromatous and reversal reaction patients
| PRJNA705463 | ENA
Project description:The immune mechanisms that control resistance vs. susceptibility to mycobacterial infection in humans were investigated by studying leprosy skin lesions, the site where the battle between the host and the pathogen is joined. Using an integrative genomics approach, we found an inverse correlation between of IFN-beta and IFN-gamma gene expression programs at the site of disease. The Type II IFN, IFN-gamma and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in the lesions from patients with the self-healing tuberculoid form of the disease and mediated antimicrobial activity against the pathogen, Mycobacterium leprae in vitro. In contrast, the Type I IFN, IFN-beta and its downstream genes, including IL-27 and IL-10, were induced in monocytes by M. leprae in vitro, and were preferentially expressed in the lesions of disseminated and progressive lepromatous form. The IFN-gamma induced macrophage antimicrobial response was inhibited by IFN-beta/IL-10, by a mechanism involving blocking the generation of bioactive 1,25-dihyroxy vitamin D as well as inhibiting induction of antimicrobial peptides cathelicidin and DEFB4. The ability of IFN-B to inhibit the IFN-gamma induced vitamin D pathway including antimicrobial activity was reversed by neutralization of IL-10, suggesting a possible target for therapeutic intervention. Finally, a common IFN-beta and IL-10 gene signature was identified in both the skin lesions of leprosy patients and in the peripheral blood of active tuberculosis patients. Together these data suggest that the ability of IFN-beta to downregulate protective IFN-gamma responses provides one general mechanism by which some bacterial pathogens of humans evade protective host responses and contribute to pathogenesis.
2013-03-05 | GSE43700 | GEO
Project description:Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.
2007-12-12 | E-GEOD-443 | biostudies-arrayexpress