文章基本信息

标题：The Trypanosoma Brucei KIFC1 Kinesin Ensures the Fast Antibody Clearance Required for Parasite Infectivity
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作者：Laurence Lecordier ; Sophie Uzureau ; Gilles Vanwalleghem 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：9
页码：1-42
DOI：10.1016/j.isci.2020.101476
语种：English
出版社：Elsevier
摘要：SummaryHuman innate immunity toTrypanosoma bruceiinvolves the trypanosome C-terminal kinesinTbKIFC1, which transports internalized trypanolytic factor apolipoprotein L1 (APOL1) within the parasite. We show thatTbKIFC1 preferentially associates with cholesterol-containing membranes and is indispensable for mammalian infectivity. Knockdown ofTbKIFC1 did not affect trypanosome growthin vitrobut 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 inTbKIFC1 knockdown cells. Clearance of surface-bound antibodies byT. bruceiis therefore essential for infectivity and depends on high membrane fluidity maintained by the cholesterol-trafficking activity ofTbKIFC1.Graphical AbstractDisplay OmittedHighlights•TheTbKIFC1 kinesin preferentially transports cholesterol-containing membranes•TbKIFC1 is absolutely required for parasite growth in mice•Cholesterol trafficking byTbKIFC1 confers high fluidity to the plasma membrane•High membrane fluidity allows antibody clearance necessary for parasite infectivityImmunology; Microbiology Parasite; Cell Biology