A Trypanosoma kinesin promotes parasite growth by triggering host arginase activity

Nzoumbou-Boko Romaric, De Muylder Géraldine, Lecordier Laurence, Dauchy Frédéric-Antoine, Holzmuller Philippe, Lemesre Jean-Loup, Bras-Gonçalves Rachel, Daulouède Sylvie, Courtois Pierrette, Beschin Alain, Pays Etienne, Vincendeau Philippe. 2018. A Trypanosoma kinesin promotes parasite growth by triggering host arginase activity. . Les Embiez : s.n., 1 poster EMBO Workshop : Molecular advances and parasite strategies in host infection, Les Embiez, France, 30 Septembre 2018/3 Octobre 2018.

Résumé : African trypanosomes can efficiently undermine the protective immune response of their hosts to favor their survival within the host and successful transmission by its vector. Excreted /secreted factors are among the first parasite molecules involved in the establishment of an environment favoring parasite settlement. We report here that factors released by the parasite promote the degradation of L-arginine through increase of arginase activity in macrophages/ myeloid cells, and antagonize NO synthases (NOS)· mediated conversion of L-arginine into NO in infected mice. Arginase induction appears to attenuate the innate response at the early stage of infection, and likely contributes to the synthesis or polyamines and the trypanosome anti-oxidant trypanothione, known to promote trypanosome growth and colonization of the host. During acute infection, a Trypanosoma brucei protein named Kinesin Heavy Chain 1 (TbKHCl) is released and sustains the development of the first (most prominent) peak or parasitaemia. TbKHCl is found to interact with SIGN-Rl at the surface of immune cells. TbKHCl modulates arginine/ NO metabolism via an IL-10-dependent induction of arginase 1 and down-regulation of iNOS activities. Consequently, IL-10/arginase 1 producing cells are impaired in their capacity to destroy the parasite, favoring parasite settlement. A kinesin modulating host arginine/NO metabolism is also detected in T. muscull, a natural murine parasite. Its neutralization during infection decreased parasite load. T. musculi kinesin showed high similarity with TbKHCl, and bioinformatics analysis revealed the presence of this gene in other trypanosomes. Thus, targeting TbKHCl may benefit the host protective immunity against T. brucei.

Mots-clés libres : Trypanosoma, Kinesin, Macrophage arginase induction

Auteurs et affiliations

• Nzoumbou-Boko Romaric, Université de Bordeaux (FRA)
• De Muylder Géraldine, ULB (BEL)
• Lecordier Laurence, ULB (BEL)
• Dauchy Frédéric-Antoine, IRD (FRA)
• Holzmuller Philippe, CIRAD-BIOS-UMR ASTRE (FRA) ORCID: 0000-0002-8919-9081
• Lemesre Jean-Loup, IRD (FRA)
• Bras-Gonçalves Rachel, IRD (FRA)
• Daulouède Sylvie, Université de Bordeaux II (FRA)
• Courtois Pierrette, Université de Bordeaux II (FRA)
• Beschin Alain, ULB (BEL)
• Pays Etienne, Université de Bordeaux II (FRA)
• Vincendeau Philippe, Université de Bordeaux II (FRA)

Source : Cirad-Agritrop (https://agritrop.cirad.fr/590409/)

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