A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity

De Muylder Géraldine, Daulouède Sylvie, Lecordier Laurence, Uzureau Pierrick, Morias Yannick, Van Den Abbeele Jan, Caljon Guy, Hérin Michel, Holzmuller Philippe, Semballa Silla, Courtois Pierrette, Vanhamme Luc, Stijlemans Benoît, De Baetselier Patrick, Barrett Michael P., Barlow Jilian L., McKenzie Andrew N.J., Barron Luke, Wynn Thomas A., Beschin Alain, Vincendeau Philippe, Pays Etienne. 2013. A Trypanosoma brucei kinesin heavy chain promotes parasite growth by triggering host arginase activity. PLoS Pathogens, 9 (10):e1003731, 14 p.

Quartile : Outlier, Sujet : PARASITOLOGY / Quartile : Outlier, Sujet : VIROLOGY / Quartile : Outlier, Sujet : MICROBIOLOGY

Résumé : Background: In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells. Methodology/Principal findings: By screening a cDNA library of T. brucei with an antibody neutralizing the arginaseinducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptordependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO) synthase activity. This TbKHC1 activity was IL-4Ra-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1- mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time. Conclusion: A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity.

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

Champ stratégique Cirad : Axe 4 (2005-2013) - Santé animale et maladies émergentes

Auteurs et affiliations

• De Muylder Géraldine, ULB (BEL)
• Daulouède Sylvie, Université de Bordeaux II (FRA)
• Lecordier Laurence, ULB (BEL)
• Uzureau Pierrick, ULB (BEL)
• Morias Yannick, ULB (BEL)
• Van Den Abbeele Jan, IMTA (BEL)
• Caljon Guy, ULB (BEL)
• Hérin Michel, Institut de Pathologie et de Génétique (BEL)
• Holzmuller Philippe, CIRAD-BIOS-UMR INTERTRYP (FRA) ORCID: 0000-0002-8919-9081
• Semballa Silla, Université de Bordeaux II (FRA)
• Courtois Pierrette, Université de Bordeaux II (FRA)
• Vanhamme Luc, ULB (BEL)
• Stijlemans Benoît, ULB (BEL)
• De Baetselier Patrick, ULB (BEL)
• Barrett Michael P., University of Glasgow (GBR)
• Barlow Jilian L., Laboratory of Molecular Biology, Medical Research (GBR)
• McKenzie Andrew N.J., Laboratory of Molecular Biology, Medical Research (GBR)
• Barron Luke, National Institute of Allergy and Infectious Diseases (USA)
• Wynn Thomas A., National Institute of Allergy and Infectious Diseases (USA)
• Beschin Alain, ULB (BEL)
• Vincendeau Philippe, Université de Bordeaux II (FRA)
• Pays Etienne, Université de Bordeaux II (FRA)

Source : Cirad - Agritrop (https://agritrop.cirad.fr/571659/)

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