Trypanosoma musculi infection in mice critically relies on mannose receptor–mediated arginase induction by a TbKHC1 kinesin H chain homolog

Nzoumbou-Boko Romaric, De Muylder Géraldine, Semballa Silla, Lecordier Laurence, Dauchy Frédéric-Antoine, Gobert Alain P., Holzmuller Philippe, Lemestre Jean-Loup, Bras-Gonçalves Rachel, Barnabé Christian, Courtois Pierrette, Daulouède Sylvie, Beschin Alain, Pays Etienne, Vincendeau Philippe. 2017. Trypanosoma musculi infection in mice critically relies on mannose receptor–mediated arginase induction by a TbKHC1 kinesin H chain homolog. Journal of Immunology, 199 (5) : 1762-1771.

Quartile : Q2, Sujet : IMMUNOLOGY

Résumé : Arginase activity induction in macrophages is an escape mechanism developed by parasites to cope with the host's immune defense and benefit from increased host-derived growth factor production. We report that arginase expression and activity were induced in macrophages during mouse infection by Trypanosoma musculi, a natural parasite of this host. This induction was reproduced in vitro by excreted/secreted factors of the parasite. A mAb directed to TbKHC1, an orphan kinesin H chain from Trypanosoma brucei, inhibited T. musculi excreted/secreted factor–mediated arginase induction. Anti-TbKHC1 Ab also inhibited T. musculi growth, both in vitro and in vivo. Induction of arginase activity and parasite growth involved C-type lectin receptors, because mannose injection decreased arginase activity induction and parasite load in vitro and in vivo. Accordingly, the parasite load was reduced in mice lacking mannose receptor C-type 1. The T. musculi KHC1 homolog showed high similarity with TbKHC1. Bioinformatics analysis revealed the presence of homologs of this gene in other trypanosomes, including pathogens for humans and animals. Host metabolism dysregulation represents an effective parasite mechanism to hamper the host immune response and modify host molecule production to favor parasite invasion and growth. Thus, this orphan kinesin plays an important role in promoting trypanosome infection, and its neutralization or the lock of its partner host molecules offers promising approaches to increasing resistance to infection and new developments in vaccination against trypanosomiasis

Mots-clés libres : Trypanosoma musculi, Mannose receptor, Macrophage arginase induction, TbKHC1 Kinesin H Chain Homolog

Classification Agris : L73 - Maladies des animaux
L72 - Organismes nuisibles des animaux

Champ stratégique Cirad : Axe 4 (2014-2018) - Santé des animaux et des plantes

Auteurs et affiliations

• Nzoumbou-Boko Romaric, Université de Bordeaux (FRA)
• De Muylder Géraldine, ULB (BEL)
• Semballa Silla, Université de Bordeaux II (FRA)
• Lecordier Laurence, ULB (BEL)
• Dauchy Frédéric-Antoine, IRD (FRA)
• Gobert Alain P., Vanderbilt University Medical Center (USA)
• Holzmuller Philippe, CIRAD-BIOS-UMR ASTRE (FRA) ORCID: 0000-0002-8919-9081
• Lemestre Jean-Loup, IRD (FRA)
• Bras-Gonçalves Rachel, IRD (FRA)
• Barnabé Christian, IRD (FRA)
• Courtois Pierrette, Université de Bordeaux II (FRA)
• Daulouède Sylvie, 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/587508/)

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