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Comparison of spatial sequencing in leprosy lesions from lepromatous and reversal reaction patients

ABSTRACT: Comparison of spatial sequencing in leprosy lesions from lepromatous and reversal reaction patients

PROVIDER: PRJNA705463 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13806007_1.fastq.gz	Fastqsanger.gz
	SRR13806007_2.fastq.gz	Fastqsanger.gz
	SRR13806008_1.fastq.gz	Fastqsanger.gz
	SRR13806008_2.fastq.gz	Fastqsanger.gz
	SRR13806009_1.fastq.gz	Fastqsanger.gz

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Comparison of spatial sequencing in leprosy lesions from lepromatous and reversal reaction patients

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.

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Comparison of single cell RNA sequencing in leprosy lesions from lepromatous and reversal reaction patients

Project description:Comparison of single cell RNA sequencing in leprosy lesions from lepromatous and reversal reaction patients

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Transcription profiling of skin lesions from leprosy samples: Divergence of macrophage phagocytic and antimicrobial programs in leprosy

Project description:Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. Here the regulation of these key functions was investigated in human blood-derived macrophages. IL-10 induced the phagocytic pathway, including CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxLDL. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of the spectrum of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form of the disease and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity in bacterial infections. Experiment Overall Design: 7 LL lesions, 10 BT lesions, 7 RR lesions

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Genome-wide expression profiling of leprosy and granuloma annulare skin lesions

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.

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Project description:we performed single-cell RNA-sequencing by Seq-Well on skin biopsy specimens from five reversal and five lepromatous patients. We obtained 21,318 cells from 10 biopsy specimens, detecting an average of 741 genes and 3,556 transcripts per cell. we recovered 12 primary cell types across all 10 samples. These annotated cell types include: T cells, B cells, plasma cells, myeloid cells, Langerhans cells, mast cells, keratinocytes, fibroblasts, smooth muscle cells, endothelial cells, eccrine gland cells and melanocytes.

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Project description:Genome-wide expression profiling of leprosy and granuloma annulare skin lesions

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