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Leishmania infantum lipophosphoglycan-deficient mutants: A tool to study host cell-parasite interplay

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Lázaro-Souza, Milena; Matte, Christine; Lima, Jonilson B.; Duque, Guillermo Arango; Quintela-Carvalho, Graziele; de Carvalho Vivarini, Áislan; Moura-Pontes, Sara; Figueira, Cláudio P.; Jesus-Santos, Flávio H.; Gazos Lopes, Ulisses; Farias, Leonardo P.; Araújo-Santos, Théo; Descoteaux, Albert; Borges, Valéria M. (2018). Leishmania infantum lipophosphoglycan-deficient mutants: A tool to study host cell-parasite interplay Frontiers in Microbiology , vol. 9 , nº 626. p. 1-10. DOI: 10.3389/fmicb.2018.00626.

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Résumé

Lipophosphoglycan (LPG) is the major surface glycoconjugate of metacyclic Leishmania promastigotes and is associated with virulence in various species of this parasite. Here, we generated a LPG-deficient mutant of Leishmania infantum, the foremost etiologic agent of visceral leishmaniasis in Brazil. The L. infantum LPG-deficient mutant (Δlpg1) was obtained by homologous recombination and complemented via episomal expression of LPG1 (Δlpg1 + LPG1). Deletion of LPG1 had no observable effect on parasite morphology or on the presence of subcellular organelles, such as lipid droplets. While both wild-type and add-back parasites reached late phase in axenic cultures, the growth of Δlpg1 parasites was delayed. Additionally, the deletion of LPG1 impaired the outcome of infection in murine bone marrow-derived macrophages. Although no significant differences were observed in parasite load after 4 h of infection, survival of Δlpg1 parasites was significantly reduced at 72 h post-infection. Interestingly, L. infantum LPG-deficient mutants induced a strong NF-κB-dependent activation of the inducible nitric oxide synthase (iNOS) promoter compared to wild type and Δlpg1 + LPG1 parasites. In conclusion, the L. infantum Δlpg1 mutant constitutes a powerful tool to investigate the role(s) played by LPG in host cell-parasite interactions.

Type de document: Article
Mots-clés libres: Leishmania infantum; Lipophosphoglycan; gene targeting; lipid droplets; macrophage
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 04 mars 2019 18:16
Dernière modification: 04 mars 2019 18:16
URI: http://espace.inrs.ca/id/eprint/7465

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