Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The b-carboline harmine is an immunomodulator in cutaneous leishmaniasis favoring the balance towards a protective immune response

ABSTRACT: Here, we investigated the impact of synthetic b-carboline harmine (ACB1801), on the immune response and pathology resulting from infection with a drug-resistant Leishmania major strain causing non-healing cutaneous lesion. Exposure to ACB1801 impacted only slightly parasite viability and parasite burden in host macrophages in vitro. However, it significantly increased MHC-II and co stimulatory molecules expression on infected DCs, suggesting enhanced immune response. Accordingly, ACB1801 monotherapy significantly decreased lesion development and parasite burden in Leishmania infected C57BL/6 mice, with similar efficacy than the widely used Amphotericin B therapy. ACB1801 impact on the immune response was validated by transcriptomics analysis showing enrichment of TNF-a, IFN-g and MHC-II Ag presentation signatures in the draining lymph nodes of treated mice. Increased frequency of protective CD4+IFN-g+TNF-α+ T cells and reduced suppressive IL-10+FoxP3- T cells was observed by flow cytometry. ACB1801 was further shown to act via the downregulation of Aryl hydroxyl receptor (AhR) signaling, decreasing immunosuppressive cytokines. Thus, these results suggest a potential use for ACB1801 alone or in combination therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE236962 | GEO | 2023/10/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

DYRK1A Inhibition via Harmine

Project description:Chemical inhibition of DYRK1A (e.g. using harmine) inhibits Th17 and promotes Treg differentiation. To better understand the mechanisms by which DYRK1A regulates Th17 differentiation, we are comparing expression profiles of naïve CD4+ T cells during the course of Th17 differentiation in the presence or absence of harmine.

2025-02-26 | GSE271205 | GEO

DYRK1A Inhibition via Harmine

Project description:DYRK1A Inhibition via Harmine

| PRJNA1130459 | ENA

High-throughout sequencing of RAW264.7 cells treated with LPS and Harmine

Project description:After stimulation of RAW264.7 cells with LPS and Harmine, high-throughput sequencing technology was used to explore the changes in the inflammation level of RAW cells and the enrichment of signaling pathways after LPS and Harmine treatment, and to find an interesting target pathway.

2024-05-20 | GSE267507 | GEO

Harmine treatment of PMA-treated J-Lat 5A8 cells

Project description:Transcriptome analysis was performed to determine what gene expression changes occur in response to treatment of the plant-derived compound harmine and to determine its effect on protein kinase C agonist reactivation of latent HIV.

2020-08-21 | GSE136172 | GEO

RNA-seq of U2OS treated with Harmine or INDY and their controls

Project description:RNA-seq was applied for identifying the change of transcriptome between U2OS cells with starvation-induced quiescence treated with Harmine Hydrochloride or INDY and the untreated controls.

2023-02-01 | GSE168401 | GEO

CCR5 promotes the migration of CD8+ T cells to the leishmanial lesions (S2W)

Project description:Cytolytic CD8+ T cells mediate immunopathology in cutaneous leishmaniasis without controlling parasites. Here, we identify factors involved in CD8+ T cell migration to the lesion that could be targeted to ameliorate disease severity.CCR5 was the most highly expressed chemokine receptor in patient lesions, and the high expression of CCL3 and CCL4, CCR5 ligands, was associated with delayed healing of lesions. To test the requirement for CCR5,Leishmania-infected Rag1-/- mice were reconstituted with CCR5-/- CD8+ T cells. We found that these mice developed smaller lesions accompanied by a reduction in CD8+ T cell numbers compared to controls. We confirmed these findings by showing that the inhibition of CCR5 with maraviroc, a selective inhibitor of CCR5, reduced lesion development without affecting the parasite burden. Together, these results reveal that CD8+ T cells migrate to leishmanial lesions in a CCR5-dependent manner and that blocking CCR5 prevents CD8+ T cell-mediated pathology.

2024-04-29 | GSE260729 | GEO

CCR5 promotes the migration of CD8+ T cells to the leishmanial lesions

Project description:Cytolytic CD8+ T cells mediate immunopathology in cutaneous leishmaniasis without controlling parasites. Here, we identify factors involved in CD8+ T cell migration to the lesion that could be targeted to ameliorate disease severity. CCR5 was the most highly expressed chemokine receptor in patient lesions, and the high expression of CCL3 and CCL4, CCR5 ligands, was associated with delayed healing of lesions. To test the requirement for CCR5, Leishmania-infected Rag1-/- mice were reconstituted with CCR5-/- CD8+ T cells. We found that these mice developed smaller lesions accompanied by a reduction in CD8+ T cell numbers compared to controls. We confirmed these findings by showing that the inhibition of CCR5 with maraviroc, a selective inhibitor of CCR5, reduced lesion development without affecting the parasite burden. Together, these results reveal that CD8+ T cells migrate to leishmanial lesions in a CCR5-dependent manner and that blocking CCR5 prevents CD8+ T cell-mediated pathology.

2024-04-29 | GSE245292 | GEO

Macrophage response towards infection by the Leishmania-viral endosymbiont duo

Project description:Leishmania RNA virus 1 (LRV1) is a double stranded RNA (dsRNA) virus found in some strains of the human protozoan parasite Leishmania, the causative agent of leishmaniasis, a neglected tropical disease. Interestingly, the presence of LRV1 inside Leishmania constitutes an important virulence factor which worsens leishmaniasis outcome in a type I interferon (type I IFN) dependent manner and contributes to treatment failure. Understanding how macrophages respond towards Leishmania alone or in combination with LRV1 as well as the role that type I IFNs may play during infection is fundamental to oversee new therapeutic strategies. In order to dissect the macrophage response towards infection, RNA Sequencing (RNA-Seq) was performed on murine wild-type (WT) bone marrow derived macrophages infected with Leishmania guyanensis (Lgy) devoid or not of LRV1 (LgyLRV1- and LgyLRV1+ respectively) or co-infected with LgyLRV1- and Lymphocytic choriomeningitis virus (LCMV) for 8 and 24 hours. Additionally, macrophages were treated with type I IFN (IFNα or IFNβ) after 6 hours of infection.

2022-05-19 | GSE203088 | GEO

The mRNA-bound proteome of Leishmania mexicana is stage-regulated with distinct transcript target pools

Project description:Leishmania species parasite infections, termed the leishmaniases, cause significant global infectious disease burden. The lifecycle of the parasite embodies three main stages that require precise coordination of gene regulation to survive drastic environmental shifts transitioning from sandfly to mammalian hosts. Constitutive transcription in these kinetoplastid parasites is overwhelmingly reliant on post-transcriptional mechanisms, yet strikingly few Leishmania trans-regulator proteins are known. Utilizing optimised crosslinking and in-depth, quantified mass spectrometry, we present a comprehensive analysis of over 1,400 mRNA binding proteins (mRBPs) and whole cell proteomes from the three main lifecycle stages.

2018-10-11 | MSV000083023 | MassIVE

Defining the transcriptional signature of healing and non-healing lesions during murine cutaneous leishmaniasis

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.

2019-02-19 | GSE56029 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data