Altmetric

Blocking synthesis of the Variant Surface Glycoprotein Coat in Trypanosoma brucei leads to an Increase in macrophage phagocytosis due to reduced clearance of surface coat antibodies

File Description SizeFormat 
journal.ppat.1006023.pdfPublished version2.35 MBAdobe PDFView/Open
Title: Blocking synthesis of the Variant Surface Glycoprotein Coat in Trypanosoma brucei leads to an Increase in macrophage phagocytosis due to reduced clearance of surface coat antibodies
Authors: Cheung, JL
Wand, NV
Ooi, CP
Ridewood, S
Wheeler, RJ
Rudenko, G
Item Type: Journal Article
Abstract: The extracellular bloodstream form parasite Trypanosoma brucei is supremely adapted to escape the host innate and adaptive immune system. Evasion is mediated through an antigenically variable Variant Surface Glycoprotein (VSG) coat, which is recycled at extraordinarily high rates. Blocking VSG synthesis triggers a precytokinesis arrest where stalled cells persist for days in vitro with superficially intact VSG coats, but are rapidly cleared within hours in mice. We therefore investigated the role of VSG synthesis in trypanosome phagocytosis by activated mouse macrophages. T. brucei normally effectively evades macrophages, and induction of VSG RNAi resulted in little change in phagocytosis of the arrested cells. Halting VSG synthesis resulted in stalled cells which swam directionally rather than tumbling, with a significant increase in swim velocity. This is possibly a consequence of increased rigidity of the cells due to a restricted surface coat in the absence of VSG synthesis. However if VSG RNAi was induced in the presence of anti-VSG221 antibodies, phagocytosis increased significantly. Blocking VSG synthesis resulted in reduced clearance of anti-VSG antibodies from the trypanosome surface, possibly as a consequence of the changed motility. This was particularly marked in cells in the G2/ M cell cycle stage, where the half-life of anti-VSG antibody increased from 39.3 ± 4.2 seconds to 99.2 ± 15.9 seconds after induction of VSG RNAi. The rates of internalisation of bulk surface VSG, or endocytic markers like transferrin, tomato lectin or dextran were not significantly affected by the VSG synthesis block. Efficient elimination of anti-VSG-antibody complexes from the trypanosome cell surface is therefore essential for trypanosome evasion of macrophages. These experiments highlight the essentiality of high rates of VSG recycling for the rapid removal of host opsonins from the parasite surface, and identify this process as a key parasite virulence factor during a chronic infection.
Issue Date: 28-Nov-2016
Date of Acceptance: 25-Oct-2016
URI: http://hdl.handle.net/10044/1/43051
DOI: http://dx.doi.org/10.1371/journal.ppat.1006023
ISSN: 1553-7374
Publisher: Public Library of Science
Journal / Book Title: Plos Pathogens
Volume: 12
Issue: 11
Copyright Statement: © 2016 The Authors. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 095161/Z/10/Z
Keywords: Virology
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status: Published
Conference Place: United States
Article Number: e1006023
Appears in Collections:Faculty of Natural Sciences



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx