Molecular signatures of anthroponotic cutaneous leishmaniasis in the lesions of patients infected with Leishmania tropica
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ABSTRACT:
PROVIDER: PRJNA894549 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22054271_1.fastq.gz | Fastqsanger.gz | |||
| SRR22054271_2.fastq.gz | Fastqsanger.gz | |||
| SRR22054272_1.fastq.gz | Fastqsanger.gz | |||
| SRR22054272_2.fastq.gz | Fastqsanger.gz | |||
| SRR22054273_1.fastq.gz | Fastqsanger.gz |
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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. 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: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:There is still no reliable human vaccination against cutaneous leishmaniasis (CL), a serious public health issue in many parts of underdeveloped nations like Morocco and Iran. There are few studies comparing the expression of immune-related genes in the skin lesions of CL patients infected with L. major and L. tropica. In this study, we used dcRT-MLPA to analyze the expression profiles of 144 immune response-related genes in CL patients from Morocco and Iran who had been exposed to L. major and L. tropica, respectively.
2024-07-01 | GSE220308 | 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: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: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.
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Project description:Leishmaniasis is a group of diseases caused by parasites of the genus Leishmania that affects millions of people worldwide. The disease outcome is determined by both the parasite species and the host's immune response. Leishmania major infection causes a localized cutaneous lesion in patients and has been widely used to study the development of T cell responses in mice. L. major infected C57BL/6 mice are resistant to infection due to the development of Th1 responses, whereas BALB/c mice develop a Th2 response resulting in disease susceptibility and failure to control parasite replication. However, these disparate host phenotypes are not observed with all Leishmania species. For example, during L. braziliensis infection both BALB/c and C57BL/6 mice are resistant. In order to better understand the host genetic basis underlying disease susceptibility in vivo, we performed a whole genome transcriptional analysis from skin lesions of BALB/c and C57BL/6 mice infected intradermally for 4 weeks with either L. braziliensis or L. major.
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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
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.
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