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Gene Expression by granuloma macrophages from resistant and susceptible mice after 4h of phagocytosis of metacyclical Leishmania major

ABSTRACT: The goal of this experiment was to identify genes which are differentially regulated between Leishmania major- infected granuloma macrophages from mice resistant (C57 Bl/6) and susceptible (BALB/c) to experimental leishmaniasis

ORGANISM(S): Mus musculus

PROVIDER: GSE127541 | GEO | 2019/10/04

REPOSITORIES: GEO

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Gene Expression by granuloma macrophages from resistant and susceptible mice after 4h of phagocytosis of metacyclical Leishmania major

Project description:Gene Expression by granuloma macrophages from resistant and susceptible mice after 4h of phagocytosis of metacyclical Leishmania major

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Leishmania major modulates autophagy in host macrophages during intracellular differentiation

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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.

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Blood transcription profiling of infections of humans with Leishmania infantum.

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Leishmania major infection-induced changes in the small RNA transcriptome of host macrophages.

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MicroRNAome comparison between macrophages infected with Leishmania RNA virus containing L.guyanensis and virus-free parasites

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

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nCounter analysis of Leishmania-infected macrophages and LT-HSC

Project description:Given the discontinuation of various first-line drugs for visceral leishmaniasis (VL), large-scale in vivo drug screening, establishment of a relapse model in rodents, immunophenotyping and transcriptomics were combined to study persistent infections and therapeutic failure. Double bioluminescent/fluorescent Leishmania infantum and L. donovani reporter lines enabled the identification of long-term hematopoietic stem cells (LT-HSC) as a niche with remarkably high parasite burdens, a feature confirmed for human hematopoietic stem cells (hHSPC). LT-HSC are more tolerant to antileishmanial drug action and serve as source of relapse. A unique transcriptional “StemLeish” signature in these cells was defined byupregulated TNF/NF-kB and RGS1/TGF-β/SMAD/SKIL signalling, and a downregulated oxidative burst.Cross-species analyses demonstrated significant overlap with human VL and HIV co-infected blood transcriptomes. In summary, the identification of LT-HSC as a drug- and oxidative stress-resistant niche,undergoing a conserved transcriptional reprogramming underlying Leishmania persistence and treatment failure, may open new therapeutic avenues for leishmaniasis.

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