The Trypanosoma Brucei KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity

Laurence Lecordier; Sophie Uzureau; Gilles Vanwalleghem; Magali Deleu; Jean-Marc Crowet; Paul Barry; Barry Moran; Paul Voorheis; Andra-Cristina Dumitru; Yoshiki Yamaryo-Botté; Marc Dieu; Patricia Tebabi; Benoit Vanhollebeke; Laurence Lins; Cyrille Y Botté; David Alsteens; Yves Dufrêne; David Pérez-Morga; Derek P Nolan; Etienne Pays

doi:10.1016/j.isci.2020.101476

The Trypanosoma Brucei KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity

iScience. 2020 Aug 20;23(9):101476. doi: 10.1016/j.isci.2020.101476. eCollection 2020 Sep 25.

Authors

Laurence Lecordier¹, Sophie Uzureau¹, Gilles Vanwalleghem¹, Magali Deleu², Jean-Marc Crowet², Paul Barry³, Barry Moran³, Paul Voorheis³, Andra-Cristina Dumitru⁴, Yoshiki Yamaryo-Botté⁵, Marc Dieu⁶, Patricia Tebabi¹, Benoit Vanhollebeke⁷, Laurence Lins², Cyrille Y Botté⁵, David Alsteens⁴, Yves Dufrêne⁴, David Pérez-Morga^{1

8}, Derek P Nolan³, Etienne Pays¹

Affiliations

¹ Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des professeurs Jeener et Brachet, 6041 Gosselies, Belgium.
² Laboratory of Molecular Biophysics at Interface (LBMI), University of Liège-Gembloux Agro Bio Tech, 2, Passage des Déportés, 5030 Gembloux, Belgium.
³ School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
⁴ Louvain Institute of Biomolecular Science and Technology, Catholic University of Louvain, Croix du Sud 4-5, 1348 Louvain-la-Neuve, Belgium.
⁵ Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble Alpes, INSERM U1209, 38700 La Tronche, France.
⁶ MaSUN, Mass Spectrometry Facility, University of Namur, 61 Rue de Bruxelles, 5000 Namur, Belgium.
⁷ Laboratory of Neurovascular Signaling, Université Libre de Bruxelles, 12, Rue des Profs Jeener et Brachet, 6041 Gosselies, Belgium.
⁸ Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles, 12, Rue des Profs Jeener et Brachet, 6041 Gosselies, Belgium.

Abstract

Human innate immunity to Trypanosoma brucei involves the trypanosome C-terminal kinesin TbKIFC1, which transports internalized trypanolytic factor apolipoprotein L1 (APOL1) within the parasite. We show that TbKIFC1 preferentially associates with cholesterol-containing membranes and is indispensable for mammalian infectivity. Knockdown of TbKIFC1 did not affect trypanosome growth in vitro but rendered the parasites unable to infect mice unless antibody synthesis was compromised. Surface clearance of Variant Surface Glycoprotein (VSG)-antibody complexes was far slower in these cells, which were more susceptible to capture by macrophages. This phenotype was not due to defects in VSG expression or trafficking but to decreased VSG mobility in a less fluid, stiffer surface membrane. This change can be attributed to increased cholesterol level in the surface membrane in TbKIFC1 knockdown cells. Clearance of surface-bound antibodies by T. brucei is therefore essential for infectivity and depends on high membrane fluidity maintained by the cholesterol-trafficking activity of TbKIFC1.

Keywords: Cell Biology; Immunology; Microbiology Parasite.