Homo sapiens
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PROVIDER: PRJNA135629 | ENA |
REPOSITORIES: ENA
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Project description:Early leukocyte response during human L. Viannia panamensis infection
| PRJNA685835 | ENA
Project description:Leishmaniasis is a disease caused by the protozoan parasite Leishmania known to affect millions of individuals worldwide. In recent years, we have established the critical role played by Leishmania zinc-metalloprotease GP63 in the modulation of host macrophage signaling and functions, favouring its survival and progression within its host. Leishmania major lacking GP63 was reported to cause limited infection in mice, however it is still unclear how GP63 may influence the innate inflammatory response and parasite survival in an in vivo context. Therefore, we were interested in analyzing the early innate inflammatory events upon Leishmania inoculation within mice and establish whether Leishmania GP63 influences this initial inflammatory response. Experimentally, L. major WT, L. major GP63 KO or L. major GP63 rescue were intraperitoneally inoculated in mice and inflammatory cells recruited were characterized microscopically and by flow cytometry (number and cell type), and their infection determined. Pro-inflammatory markers such as cytokines, chemokines and extracellular vesicles (EVs, e.g. exosomes) were monitored and proteomic analysis was performed on exosome contents. Data obtained from this study suggest that Leishmania GP63 does not significantly influence the pathogen-induced inflammatory cell recruitment, but rather their activation status and effector function. Concordantly, internalization of promastigotes during early infection could be influenced by GP63 as less L. major KO amastigotes were found within host cells and appear to maintain in host cells over time. Collectively this study provides a clear analysis of innate inflammatory events occurring during L. major infection and further establish the prominent role of the virulence factor GP63 to provide favorable conditions for host cell infection.
2022-01-01 | GSE189385 | GEO
Project description:Minor structural variation and complex clonal genomic structure in Leishmania (Viannia) panamensis
| PRJEB35090 | ENA
Project description:Leishmania (Viannia) braziliensis is a parasite prevalent in Brazil and associated with tegumentary leishmaniasis (TL), including cutaneous (CL) and mucosal (ML) forms. The mechanisms of pathogenesis of TL are not fully understood, including some factors related to the host and parasite interaction in response to infection, and especially about Leishmania RNA Virus 1 (LRV1), an endosymbiont virus parasitizing Leishmania species, particularly triggers ML. Molecular approaches are usually applied to compare situations and to understand these interactions. Here, microarray analysis identified 162 differentially expressed genes in LbLRV1+ vs. LbLRV1- infection, with 126 upregulated genes related to IFN signaling, OAS/RNAse L, vitamin D3, and RIG-I type receptors. Additionally, 36 down-regulated genes were observed. Then, two validation assays were performed to confirm these results (RT-qPCR and Cytometric Bead Array). The main results comprise the differential gene expression in cells infected with LbLRV1+ compared to LbLRV1- and control, with overexpression of various genes in LbLRV1+ cells. Cytokine levels showed no significant differences between LbLRV1+ and LbLRV1-. This study highlighted the activation of the OAS/RNase L signaling pathway and the non-genomic actions of vitamin D3 in LbLRV1+ infection compared to LbLRV1- and control. This research contributes to our understanding of the immune response and molecular pathways involved in Leishmania infections, particularly in the presence of LRV1. We used microarrays to detail the global gene expression program underlying infection of human mnocyte-derived macrophages with LbLRV1-, LbLRV1+ and identified distinct classes of genes upregulated during this process.
2024-04-06 | GSE247487 | GEO
Project description:Transcriptomic Dynamics of Human Macrophage Response to Leishmania major infection
| PRJNA186954 | ENA
Project description:Leishmania (L.) are obligated intracellular protozoan parasites that develop electively in macrophages. These cells that are acting as a safe shelter for the pathogens but also as their ultimate killer, making them the alpha and the omega during leishmaniasis diseases. Macrophages are able to secrete a remarkably diverse set of regulators known to influence the physiological functions and differentiation of neighboring cells to trigger an adaptive immune response of protective Th1-type cells, whereas parasites have developed a wide range of mechanisms to circumvent the hostâs immune responses. Most of our understanding of this host-parasite conflict, in the context of macrophage invasion by L. major metacyclic promastigotes, has been gleaned from studies investigating the macrophage responses at late and unique time points after infection. To investigate the dynamics of this duel, we have analyzed the transciptomic profile of monocyte-derived human macrophages at different time points during the first 24h upon in vitro infection using high throughput microarray platform. The gene expression profile of 17,838 genes showed high expression variability between the three human donors at different time points post infection. Cross comparison between the three donors allowed the identification of a common set of expressed genes coding for inflammatory and chemotactic molecules, transcription factors, apoptosis inhibition, glucose synthesis and heme metabolism. The findings presented in this work suggest that transcriptome dynamics of macrophages early during the first 24h post infection enable to identify novel key pathways deregulated upon L. major invasion. Our reported set of expressed genes will be useful in future rounds of data mining and functional analyses. In total 27 samples from three different donors were analyzed. For each donor, samples at 0h, 3h, 6h, 12h and 24h of culture were used as controls. For each donor, samples of cells infected with metacyclic Leishmania major parasites at 3h, 6h, 12h and 24h post-infection were analyzed.
2015-12-31 | E-GEOD-43661 | biostudies-arrayexpress
Project description:Transcriptional profile of human monocyte-derived macrophages infected with L.(V.)panamensis was compared to the profile of uninfected cells to delineate transcriptional activation triggered by the infection. two condition experiment: human monocyte-derived macrophages infected with L.(V.)panamensis. 6-5 donors per time point. 3 times point. 1-3 replicates per donor-time point.
2012-12-25 | E-GEOD-25819 | biostudies-arrayexpress
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
Project description:Transcriptional profile of human monocyte-derived macrophages infected with L.(V.)panamensis was compared to the profile of uninfected cells to delineate transcriptional activation triggered by the infection.
2012-12-25 | GSE25819 | GEO
Project description:Protozoa of the genus Leishmania are the causative agents of leishmaniasis in humans. These parasites cycle between promastigotes in the sand fly mid-gut and amastigotes in phagolysosome of mammalian macrophages. During infection, host up-regulate nitric oxide synthase and parasite induce host arginase expression, both of which use arginine as a substrate. These elevated activities deplete macrophage arginine pools, a situation that invading Leishmania must overcome since it is an essential amino acid. Leishmania donovani imports exogenous arginine via a mono-specific amino acid transporter (AAP3) and utilizes it primarily through the polyamine pathway to provide precursors for trypanothione biosynthesis. Here we report the discovery of a pathway whereby promastigote and amastigote forms of the Leishmania sense the lack of environmental arginine and respond with rapid up-regulation in AAP3 expression and activity, as well as several other transporters. Significantly, this arginine deprivation response is also activated in parasites during macrophage infection. Phosphoproteomic analyses of L. donovani promastigotes have implicated a Mitogen-Activated Protein Kinase 2 (MPK2)-mediated signaling cascade in this response and L. mexicana mutants lacking MPK2 are unable to respond to arginine deprivation. In this study, we established that Leishmania cells sense the absence of arginine in their environment; both in culture (axenic promastigotes and amastigotes) and in macrophages during infection (amastigotes). This study describes the first amino acid deprivation sensing mechanism and the pathway that transduce this response, and reveals a novel host-pathogen metabolic interplay. Total RNA from Ten Leishmania donovani samples were analyzed using RNA-Seq. Cells from two life stages (promastigotes and amastigotes) were grown in axenic culture in the presence and absense of arginine. For each condition two biological replicates were grown and analyzed. In addition two macrophage grown amastigotes were analyzed.
2016-08-01 | E-GEOD-71572 | biostudies-arrayexpress