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
Affiliations
Laurence Lecordier
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des professeurs Jeener et Brachet, 6041 Gosselies, Belgium
Sophie Uzureau
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des professeurs Jeener et Brachet, 6041 Gosselies, Belgium
Gilles Vanwalleghem
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des professeurs Jeener et Brachet, 6041 Gosselies, Belgium
Magali Deleu
Laboratory of Molecular Biophysics at Interface (LBMI), University of Liège-Gembloux Agro Bio Tech, 2, Passage des Déportés, 5030 Gembloux, Belgium
Jean-Marc Crowet
Laboratory of Molecular Biophysics at Interface (LBMI), University of Liège-Gembloux Agro Bio Tech, 2, Passage des Déportés, 5030 Gembloux, Belgium
Paul Barry
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland
Barry Moran
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland
Paul Voorheis
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland
Andra-Cristina Dumitru
Louvain Institute of Biomolecular Science and Technology, Catholic University of Louvain, Croix du Sud 4-5, 1348 Louvain-la-Neuve, Belgium
Yoshiki Yamaryo-Botté
Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble Alpes, INSERM U1209, 38700 La Tronche, France
Marc Dieu
MaSUN, Mass Spectrometry Facility, University of Namur, 61 Rue de Bruxelles, 5000 Namur, Belgium
Patricia Tebabi
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des professeurs Jeener et Brachet, 6041 Gosselies, Belgium
Benoit Vanhollebeke
Laboratory of Neurovascular Signaling, Université Libre de Bruxelles, 12, Rue des Profs Jeener et Brachet, 6041 Gosselies, Belgium
Laurence Lins
Laboratory of Molecular Biophysics at Interface (LBMI), University of Liège-Gembloux Agro Bio Tech, 2, Passage des Déportés, 5030 Gembloux, Belgium
Cyrille Y. Botté
Institute for Advanced Biosciences, CNRS UMR5309, Université Grenoble Alpes, INSERM U1209, 38700 La Tronche, France
David Alsteens
Louvain Institute of Biomolecular Science and Technology, Catholic University of Louvain, Croix du Sud 4-5, 1348 Louvain-la-Neuve, Belgium
Yves Dufrêne
Louvain Institute of Biomolecular Science and Technology, Catholic University of Louvain, Croix du Sud 4-5, 1348 Louvain-la-Neuve, Belgium
David Pérez-Morga
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des professeurs Jeener et Brachet, 6041 Gosselies, Belgium; Center for Microscopy and Molecular Imaging (CMMI), Université Libre de Bruxelles, 12, Rue des Profs Jeener et Brachet, 6041 Gosselies, Belgium
Derek P. Nolan
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland; Corresponding author
Etienne Pays
Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des professeurs Jeener et Brachet, 6041 Gosselies, Belgium; Corresponding author
Summary: 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.
