Mus musculus
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ABSTRACT:
PROVIDER: PRJNA242643 | ENA |
REPOSITORIES: ENA
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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
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:Molecular signature of healing in cutaneous leishmaniasis
| PRJNA978060 | ENA
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.
2014-03-07 | GSE55664 | GEO
Project description:The microbiological signature of human cutaneous leishmaniasis lesions
| PRJNA267573 | ENA
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
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:In addition to the recently published in situ transcriptomics of LCL skin lesions (Novais et al., Khouri et al.), we herein present the first systemic disease signature of localized cutaneous leishmaniasis (LCL), using Affymetrix microarrays (HuGene 1.0) followed by systems biology analysis of the PBMC transciptome of LCL patients (n=18), as compared to healthy controls (n=12).
2017-09-15 | GSE80008 | GEO
Project description:Cutaneous leishmaniasis is a localized infection controlled by CD4+ T cells that produce IFN-g within lesions. Phagocytic cells recruited to lesions, such as monocytes, are then exposed to IFN-g which triggers their ability to kill the intracellular parasites. Consistent with this, a transcriptional analysis of lesions from patients identified the presence of a strong interferon stimulated gene (ISG) signature. To determine what systemic responses are occurring that might influence the disease, we performed RNA sequencing (RNA-seq) on the blood of L. braziliensis-infected patients, as well as healthy controls. Functional enrichment analysis identified a transcriptional ISG signature as the dominant response in the blood of patients. An increase in monocytes and macrophages in the blood, estimated from our RNA-seq dataset, was positively correlated with this ISG signature. Consistent with this result, patients had circulating IFN-g in their serum. A cytotoxicity signature, which is a dominant feature in the lesions, was also found in the blood and correlated with an increased abundance of cytolytic cells. Thus, two transcriptional signatures present in lesions were found systemically, although with a substantially reduced number of differentially expressed genes (DEGs). Finally, we found that the number of DEGs and ISGs in leishmaniasis was similar to tuberculosis – another localized infection – but significantly less than observed in malaria. In contrast, the cytolytic signature and increased cytolytic cell abundance was not found in tuberculosis or malaria. Our results indicate that systemic signatures can reflect what is occurring in leishmanial lesions. Furthermore, the presence of an ISG signature in blood monocytes and macrophages suggests that when these cells enter lesions they may already be primed to control the parasites.
2021-03-23 | GSE162760 | GEO
Project description:As a vector-borne disease, leishmaniasis is caused by a parasitic protozoans of leishmania genus and transmitted by female Phlebotomine sandflies. Depending on the body location where immotile form of the parasite namely amastigote is proliferated, three main clinical forms as cutaneous, muco-cutaneous and visceral leishmaniases are defined. While manifestation of cutaneous leishmaniasis is skin lesions on the exposed part of the body, enlarged lymph nodes, spleen or liver along with fever, fatigue and weight loss are the symptoms of visceral leishmaniasis. The most dangerous form is visceral leishmaniasis since it may end up with fatalities if patients are not treated. The purpose of this study was to investigate the difference between the protein expression profiles of leishmania isolates obtained from visceral and cutaneous leishmaniasis patients. To compare two sample groups to each other genetically, L.infantum was chosen since it causes both visceral and cutaneous leishmaniasis. Additionally, another sample group as cutaneous leishmaniasis caused by L.tropica was included to make the comparison both intra- and interspecies level. For protein profiling, both gel-based and gel-free proteomic approaches were carried out. In brief, a total of 15 samples, 5 from each group, were separated on pI 3-10 2D-PAGE gel. Additionally, 9 of those 15 samples, 3 from each group, were analyzed according to qualitative shotgun proteomics method and differential proteins were determined by drawing venn diagram.
2022-01-14 | PXD016333 | Pride