Systemic disease signature of human cutaneous leishmaniasis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE80008 | GEO | 2017/09/15
SECONDARY ACCESSION(S): PRJNA317617
REPOSITORIES: GEO
Similar Datasets
Project description:We evaluated the trancriptome of primary cutaneous leisions caused by infection with Leishmania braziliensis. mRNA-seq technique was used to study the trancriptome of both host and parasite. A total of 10 samples was obtained from primary skin ulcers of two extreme clinical forms of American tegumentary leishmaniasis: (i) individuals that after antimonial treatment cured completely (localized cutaneous leishmaniasis - LCL, n=5) and (ii) individuals that developed mucosal lesions in naso and oropharynx areas long after initial healing of the cutaneous lesion (mucosal leishmaniasis - ML, n=5). The sequencing generated an average of 13+ 5 million reads per samples. The reads were aligned to Homo sapiens (USCS - hg19) and to Leishmania braziliensis (Wellcome Trust Sanger Institute - V2_29072008) genomes. Approximately, 15,000 human genes could be detected in the samples. Low amount of L. braziliensis reads did not allow the evaluation of parasite gene expression. LCL and ML samples showed different patterns of gene expression, indicating a more robust immune response in LCL individuals. In summary, this study demonstrated that next-generation sequencing can be used for identification of potentially important biological pathways and drug targets in the host-response to L. braziliensis infection and for characterization of a gene expression signature that could be used to predict the disease outcome. Moreover, we also showed the ability of this technique in, simultaneously, sequence host and pathogen mRNA. Examination of 10 fragments of cutaneous lesions: 5 from localized cutaneous leishmaniasis patients and 5 from mucosal leishmaniasis patients.
2012-10-24 | E-GEOD-33601 | biostudies-arrayexpress
Project description:We evaluated the trancriptome of primary cutaneous leisions caused by infection with Leishmania braziliensis. mRNA-seq technique was used to study the trancriptome of both host and parasite. A total of 10 samples was obtained from primary skin ulcers of two extreme clinical forms of American tegumentary leishmaniasis: (i) individuals that after antimonial treatment cured completely (localized cutaneous leishmaniasis - LCL, n=5) and (ii) individuals that developed mucosal lesions in naso and oropharynx areas long after initial healing of the cutaneous lesion (mucosal leishmaniasis - ML, n=5). The sequencing generated an average of 13+ 5 million reads per samples. The reads were aligned to Homo sapiens (USCS - hg19) and to Leishmania braziliensis (Wellcome Trust Sanger Institute - V2_29072008) genomes. Approximately, 15,000 human genes could be detected in the samples. Low amount of L. braziliensis reads did not allow the evaluation of parasite gene expression. LCL and ML samples showed different patterns of gene expression, indicating a more robust immune response in LCL individuals. In summary, this study demonstrated that next-generation sequencing can be used for identification of potentially important biological pathways and drug targets in the host-response to L. braziliensis infection and for characterization of a gene expression signature that could be used to predict the disease outcome. Moreover, we also showed the ability of this technique in, simultaneously, sequence host and pathogen mRNA.
2012-10-24 | GSE33601 | GEO
Project description:The aim of this study was to identify differences in the NK-cell response towards Leishmania mexicana lipophosphoglycan (LPG) between patients with localized (LCL) and diffuse (DCL) cutaneous leishmaniasis through gene expression profiling, in an attempt to pinpoint alterations in the signaling pathways responsible for the NK-cell dysfunction in patients with DCL. To determine the gene expression profiling in non stimulated and LPG-stimulated NK cells we include samples of controls, LCL and DCL patients. We performed microarrays (Human Gene 1.0 ST, Affymetrix) to identify differentially expressed transcripts between non stimulated and LPG-stimulated NK cells between controls, LCL and DCL samples.
2016-01-01 | GSE69252 | GEO
Project description:Whole blood transcriptomes taken from patients with cutaneous leishmaniasis at presentation and during sodium stibogluconate treatment.
2021-07-21 | GSE180379 | GEO
Project description:Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8 T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8 T cell differentiation, was driven by hypoxia within the inflamed skin. Hypoxia was further enhanced by the recruitment of neutrophils that consumed oxygen to produce reactive oxygen species and ultimately increased the hypoxic state and granzyme B expression in CD8 T cells. Importantly, lesions from cutaneous leishmaniasis patients exhibited hypoxia transcription signatures that correlated with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T cells contribute to pathogenesis.
2024-04-29 | GSE193005 | GEO
Project description:Among the most central questions in Leishmania research is why some species remain in the skin dermis at the site of infection by the sand fly vector whereas other species migrate to visceral organs where they cause fatal visceral leishmaniasis. Although L. donovani is the species typically responsible for visceral leishmaniasis, an atypical L. donovani strain is the etiologic agent for cutaneous leishmaniasis in Sri Lanka. To identify molecular determinants for visceral disease, we have analysed the phenotype and genotype of two L. donovani clinical isolates from Sri Lanka where one isolate was derived from a cutaneous leishmaniasis patient (CL) and the other from a visceral leishmaniasis patient (VL). These isolates cause dramatically different pathology when introduced into mice; notably the CL isolate has lost the ability to survive in visceral organs while the VL isolate was highly virulent in visceral organs of BALB/c mice. Whole genome sequencing of the CL and VL isolates revealed that these genomes were very similar as there were no gene deletions and few individual gene amplifications. Indels resulting in frame shifts and loss/gain of stop codons resulted in 13 distinct pseudogenes present in each of the CL and VL isolates. There were 154 non-synonymous SNPs specific to the CL isolate and 193 non-synonymous SNPs specific to the VL isolate. Genome wide gene expression analysis revealed several transcript level differences, including the A2 virulence gene resulting in higher expression of A2 proteins in the VL isolate than in the CL isolate. Genotypic variations relevant to pathology and tropism in Leishmania can be interrogated by reverse genetics. Experimentally increasing A2 expression in the CL isolate through gene transfer significantly increased itM-bM-^@M-^Ys ability to survive in the spleen of BALB/c mice and conversely, down-regulating A2 expression in the VL isolate abrogated attenuated its survival in BALB/c mice. These observations reveal that there are relatively few genetic differences between the CL and VL isolates apart from the A2 genes, but collectively these have profound effects on human disease and experimentally infected mice. 6 Samples in total, 3 each from VL and CL causing isolates were analyzed by Splice Leader RNASeq. These three samples from each of the isolates were grown to form one of the following three lifestages, Promastigotes, Macrophage derived Amastigotes, Axenic Amastigotes.
2013-12-31 | E-GEOD-48475 | biostudies-arrayexpress
Project description:Among the most central questions in Leishmania research is why some species remain in the skin dermis at the site of infection by the sand fly vector whereas other species migrate to visceral organs where they cause fatal visceral leishmaniasis. Although L. donovani is the species typically responsible for visceral leishmaniasis, an atypical L. donovani strain is the etiologic agent for cutaneous leishmaniasis in Sri Lanka. To identify molecular determinants for visceral disease, we have analysed the phenotype and genotype of two L. donovani clinical isolates from Sri Lanka where one isolate was derived from a cutaneous leishmaniasis patient (CL) and the other from a visceral leishmaniasis patient (VL). These isolates cause dramatically different pathology when introduced into mice; notably the CL isolate has lost the ability to survive in visceral organs while the VL isolate was highly virulent in visceral organs of BALB/c mice. Whole genome sequencing of the CL and VL isolates revealed that these genomes were very similar as there were no gene deletions and few individual gene amplifications. Indels resulting in frame shifts and loss/gain of stop codons resulted in 13 distinct pseudogenes present in each of the CL and VL isolates. There were 154 non-synonymous SNPs specific to the CL isolate and 193 non-synonymous SNPs specific to the VL isolate. Genome wide gene expression analysis revealed several transcript level differences, including the A2 virulence gene resulting in higher expression of A2 proteins in the VL isolate than in the CL isolate. Genotypic variations relevant to pathology and tropism in Leishmania can be interrogated by reverse genetics. Experimentally increasing A2 expression in the CL isolate through gene transfer significantly increased it’s ability to survive in the spleen of BALB/c mice and conversely, down-regulating A2 expression in the VL isolate abrogated attenuated its survival in BALB/c mice. These observations reveal that there are relatively few genetic differences between the CL and VL isolates apart from the A2 genes, but collectively these have profound effects on human disease and experimentally infected mice.
2013-12-31 | GSE48475 | GEO
Project description:The aim of this study was to identify differences in the NK-cell response towards Leishmania mexicana lipophosphoglycan (LPG) between patients with localized (LCL) and diffuse (DCL) cutaneous leishmaniasis through gene expression profiling, in an attempt to pinpoint alterations in the signaling pathways responsible for the NK-cell dysfunction in patients with DCL. To determine the gene expression profiling in non stimulated and LPG-stimulated NK cells we include samples of controls, LCL and DCL patients. We performed microarrays (Human Gene 1.0 ST, Affymetrix) to identify differentially expressed transcripts between non stimulated and LPG-stimulated NK cells between controls, LCL and DCL samples. Human NK cells from controls, LCL and DCL patients were divided in two conditions: non stimulated and LPG-stimulated (6h) cells, different number of biological replicates were analyzed: four replicates for controls, two replicates for LCL and 3 replicates for DCL patients samples with a total of 18 microarrays.
2016-07-03 | E-GEOD-69252 | biostudies-arrayexpress
Project description:Cutaneous leishmaniasis (CL) is prevalent in many low-income countries. Although CL is considered non-fatal, it has a major impact on public health systems of affected nations, causing social and economic problems due to disfiguration, morbidity, loss of productivity and medical costs for the public sector. Since no effective human vaccine against CL exists, it is crucial to understand better factors that may affect the outcome of the disease, including the impact of the pathogen on the host immune system. While transcriptomics analyses of the skin lesion in CL patients were recently reported, there is a dearth of information on the expression of immune-related genes in the blood of CL patients. We herein sought to profile the expression of immune-related genes in the blood of healed, asymptomatic and active CL patients.
2022-07-27 | GSE197222 | GEO
Project description:In this study employed a systems analysis approach to study molecular signatures of cutaneous leishmaniasis (CL) caused by Leishmania tropica (L. tropica) in the skin lesions of ulcerativeCL (UCL) and non-ulcerative CL( NUCL) patients. Results from RNA-seq analysis determined shared and unique functional transcriptional pathways in the lesions of the UCL and Nucl patients. Several transcriptional pathways involved in inflammatory response were positively enriched in the CL lesions. These results enhance our understanding of human skin response to CL caused by L. tropica.
2022-11-01 | GSE216638 | GEO