The Role of Leishmania GP63 in Modulation of Innate Inflammatory Response to Leishmania major Infection
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PROVIDER: PRJNA782881 | ENA |
REPOSITORIES: ENA
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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.
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Project description:Leishmania major: Sir2rp3 overexpressor vs wild-type
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Project description:Comparative Genomic Hybridization of Leishmania major SbIII resistant mutants and L. major WT
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Project description:Autophagy generally participates in innate immunity by elimination of intracellular pathogens. However, many of them developed successful strategies to counteract their autolysosomal digestion and lastly to exploit this catabolic cellular process. Protozoan parasites of the genus Leishmania are the causative agent of leishmaniasis, one of the 13 most important tropical diseases. Leishmania persists as endo-parasite in host macrophages, where it uses multiple strategies to manipulate the microbicidal host cell functions and to escape from the host immune system. Understanding how Leishmania interacts with host macrophages during uptake, differentiation, intracellular replication, and release might be the key to develop new drugs in target-directed approaches to treat patient with leishmaniasis. Here, we generated expression profiles from bone marrow-derived macrophages (BMDM) at 1h and 24h post infection (p.i.) with Leishmania major and respective controls.
2015-08-03 | E-GEOD-52624 | biostudies-arrayexpress
Project description:Murine bone marrow derived macrophages were infected with Leishmania major or Leishmania donovania promastigotes, allowed to phagocytose latex beads or not treated. Gene expression profiles were compared to identify i) the effect of Leishmania infection; ii) the differences in effects between L. major and L. donovani; and iii) the effect of pahgocytosis of latex beads.
2008-02-05 | E-MEXP-1254 | biostudies-arrayexpress
Project description:Kinetoplastid-specific histone variant functions are conserved in Leishmania major
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Project description:The genomic DNAs of strains JPCM5 and 263 of L. infantum, strains LV39 and Friedlin of L. major and strains Parrot-TarII and S125 of L. tarentolae were used in comparative genomic hybridizations to reveal the intra-species and inter-species gene content, and to validate L. tarentolae Parrot-TarII genome sequencing results. Leishmania (Sauroleishmania) tarentolae was first isolated in the lizard Tarentola mauritanica. This species is not known to be pathogenic to humans but is often used as a model organism for molecular analyses or protein overproduction. The Leishmania tarentolae Parrot-TarII strain genome sequence was resolved by high-throughput sequencing technologies. The L. tarentolae genome was first assembled de novo and then aligned against the reference L. major Friedlin genome to facilitate contig positioning and annotation, providing a 23-fold coverage of the genome. This is the first non-pathogenic to humans kinetoplastid protozoan genome to be described, and it provides an opportunity for comparison with the completed genomes of the pathogenic Leishmania species. A high synteny was observed in de novo assembled contigs between all sequenced Leishmania species. A number of limited chromosomal regions diverged between L. tarentolae and L. infantum, while remaining syntenic with L. major. Globally, over 90% of the L. tarentolae gene content was shared with the other Leishmania species. There were 250 L. major genes absent from L. tarentolae, and interestingly these missing genes were primarily expressed in the intracellular amastigote stage of the pathogenic parasites. This implies that L. tarentolae may have impaired ability to survive as an intracellular parasite. In contrast to other Leishmania genomes, two gene families were expanded in L. tarentolae, namely the leishmanolysin (GP63) and a gene related to the promastigote surface antigen (PSA31C). Overall, L. tarentolae appears to have a gene content more adapted to the insect stage rather than the mammalian one. This may partly explain its inability to replicate within mammalian macrophages and its suspected preferred life style as promastigote in the lizards.
2011-10-21 | GSE27184 | GEO
Project description:Leishmania major isolate:HUM1 Genome sequencing
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