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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of cutaneous lesions caused by Leishmania braziliensis and normal skin.

ABSTRACT: This study was carried out to evaluate the changes that occur in the skin after the development of cutaneous leishmaniasis, aiming at a comprehensive understanding of immune pathways and biological functions activated in lesions caused by L. braziliensis. This analysis was conducted on 8 skin ulcers from patients infected with L. braziliensis. The patients selected for the gene expression analysis had recent L. braziliensis infection that had not yet been treated. 8 controls samples are skin biopsies from healthy donors (non-infected).

ORGANISM(S): Homo sapiens

SUBMITTER: Pablo Oliveira

PROVIDER: E-GEOD-63931 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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CD8 T cells induce perforin-dependent pathology in Leishmania braziliensis infection

Project description:The mechanisms that mediate immunopathologic responses in infectious diseases are often less well understood than how the pathogens are controlled. Here, we have investigated what causes increased pathology following infection with the protozoan parasite, Leishmania braziliensis. We focused on CD8 T cells since their presence in leishmanial lesions has been correlated with increased disease. By adoptively transferring CD8 T cells to L. braziliensis infected RAG mice, we found that unregulated CD8 T cells promote severe pathology at the infection site, as well as the development of metastatic lesions in other skin sites. In mice with severe pathology, we visualized CD8 T cells degranulating and lysing L. braziliensis infected cells, and in parallel studies with L. braziliensis patients we confirmed that CD8 T cells within lesions exhibit a cytolytic phenotype. We found that perforin deficient CD8 T cells failed to induce disease, indicating that the increased disease induced by CD8 T cells was due perforin-dependent cytotoxicity. In contrast, although we found that CD8 T cells made both IFN-γ and IL-17, neither of these cytokines is required for the development of pathology. Thus, we show for the first time that immunopathology in leishmaniasis can be mediated by cytolytic CD8 T cells. Twelve skin biopsy samples were analyzed, including 2 normal skin biopsies obtained from patients in N. America, and 10 skin biosies obtained from Leishmania brazilensis infected patients presenting at the Corte de Pedra Health Post in Corte de Pedra, Bahia, Brazil

2013-07-08 | E-GEOD-43880 | biostudies-arrayexpress

Differential gene expression between uninfected and infected U937 derived macrophages with Leishmania braziliensis

Project description:The main objective of this study is to identify the list of genes differentially expressed between infected with Leishmania braziliensis and non-infected macrophage cultures based on gene expression microarray profiling The dataset is comprised by the expression profile of 6 samples from three independent experiments and each experiment had three technical replicates. 3 of the 6 samples were U937 derived macrophages infected by Leishmania braziliensis and the other 3 were U937 derived macrophages without infection with Leishmania braziliensis. A total of 18 microarrays analysis were performed.

2015-06-10 | E-GEOD-61211 | biostudies-arrayexpress

Genomic profiling of human Leishmania braziliensis lesions identifies transcriptional modules associated with cutaneous immunopathology

Project description:The host immune response plays a critical role not only in protection from human leishmaniasis, but also in promoting disease severity. Although candidate gene approaches in mouse models of leishmaniasis have been extremely informative, a global understanding of the immune pathways active in lesions from human patients is lacking. To address this issue, genome-wide transcriptional profiling of Leishmania braziliensis-infected cutaneous lesions and normal skin controls was carried out. A signature of the L. braziliensis skin lesion was defined that includes over 2,000 differentially regulated genes. Pathway-level analysis of this transcriptional response revealed key biological pathways, as well as specific genes, associated with cutaneous pathology, generating a testable 'metapathway' model of immune-driven lesion pathology, and providing new insights for treatment of human leishmaniasis. Thirty-five skin biopsies were analyzed, including 10 normal skin biopsies (2 from North America and 8 from non-endemic area in Brazil), and 25 skin lesion biopsies (8 early cutaneous lesions, 17 late cutaneous lesions) obtained from Leishmania brazilensis-infected patients presenting at the Corte de Pedra Health Post in Corte de Pedra, Bahia, Brazil.

2014-03-07 | E-GEOD-55664 | biostudies-arrayexpress

Transcription profiling of cutaneous lesions caused by Leishmania braziliensis and normal skin.

Project description:This study was carried out to evaluate the changes that occur in the skin after the development of cutaneous leishmaniasis, aiming at a comprehensive understanding of immune pathways and biological functions activated in lesions caused by L. braziliensis.

2015-02-01 | GSE63931 | GEO

Genomic profiling of human Leishmania braziliensis lesions identifies transcriptional modules associated with cutaneous immunopathology

2014-03-07 | GSE55664 | GEO

CD8 T cells induce perforin-dependent pathology in Leishmania braziliensis infection

2013-07-08 | GSE43880 | GEO

Leishmania braziliensis

Project description:Leishmania braziliensis Genome sequencing

| PRJNA475480 | ENA

Leishmania braziliensis

Project description:Leishmania braziliensis Genome sequencing and assembly

| PRJNA292004 | ENA

Leishmania braziliensis Protein Arginine Methyltransferases interactomes

Project description:We functionally characterized the five predicted PRMTs in Leishmania braziliensis by gene knockout and endogenous protein HA tagging using CRISPR/Cas9 gene editing. We report that R-methylation profiles vary among Leishmania species and across L. braziliensis lifecycle stages, with the peak PRMT expression occurring in promastigotes. A list of PRMT-interacting proteins was obtained in a single coimmunoprecipitation assay using HA-tagged PRMTs, suggesting a network of putative targets of PRMTs and cooperation between the R-methylation writers. Knockout of each L. braziliensis PRMT led to significant changes in global arginine methylation patterns without affecting cell viability. Deletion of either PRMT1 or PRMT3 disrupted most type I PRMT activity, resulting in a global increase in monomethyl arginine levels. Using anti-MMA antibodies, we performed an IP experiment to identify MMA proteins in the parental line, single PRMT1 knockout, PRMT1/PRMT7 double knockout and PRMT1-Addback parasites. The results indicate that R-methylation is modulated across lifecycle stages in L. braziliensis and show possible functional overlap and cooperation among the different PRMTs in targeting proteins. Overall, our data suggest important regulatory roles of these proteins throughout the L. braziliensis life cycle, showing that arginine methylation is important for parasite-host cell interactions. Linked publication: https://doi.org/10.1101/2021.09.22.461376.

2022-03-03 | PXD031057 | Pride

Characterization of differentially abundant proteins among Leishmania (Viannia) braziliensis strains isolated from atypical or typical lesions

Project description:Leishmania (Viannia) braziliensis is the main etiological agent of cutaneous and mucocutaneous leishmaniasis in Latin America. Reports have described non-ulcerated atypical tegumentary leishmaniasis cases caused by L. braziliensis in several regions of the world, including in patients from the Xacriabá Indigenous reserve, in São João das Missões/Minas Gerais - Brazil. Parasites isolated from these atypical clinical lesions have previously been found to be resistant to antimony-based therapeutics. In the present study, proteins displaying differential abundance in 2 strains of L. braziliensis isolated from patients with atypical lesions compared with 4 strains isolated from patients with typical lesions were identified using a quantitative proteomics approach based on tandem mass tag labeling (TMT) and mass spectrometry. A total of 532 (p value <0.05) differentially abundant proteins were identified (298 up-regulated and 234 down-regulated) in strains from atypical lesions compared to strains from typical lesions. We observed a variety of proteins with differential abundance among the studied strains. Prominent positively regulated in atypical strains included proteins which may confer a greater survival inside the macrophage, proteins related to resistance to antimony and higher peroxidase activity. Also were identified proteins suggest as new drug and vaccines target. Our data contribute to characterization of these intriguing L. braziliensis strains, and sheds new light on ACL cases has been associated with therapeutic failures.

2022-02-11 | PXD029995 | Pride

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