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

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

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.

langue originaleAnglais
Numéro d'article101476
journaliScience
Volume23
Numéro de publication9
Date de mise en ligne précoce2020
Les DOIs
Etat de la publicationPublié - 25 sept. 2020

Empreinte digitale Examiner les sujets de recherche de « The Trypanosoma Brucei KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity ». Ensemble, ils forment une empreinte digitale unique.

Contient cette citation