A Novel Mechanism of Bacterial Toxin Transfer within Host Blood Cell-Derived Microvesicles

PLoS Pathogens

Ann-Charlotte Kristoffersson¹  Sebastian Loos¹  Ida Arvidsson¹  Johan Rebetz¹  Zivile D. Békássy¹  Milan Chromek¹  Karl E. Johansson¹  Diana Karpman¹  Anne-lie Ståhl¹  Matthias Mörgelin² 

[1] Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden;Division of Infection Medicine, Clinical Sciences Lund, Lund University, Lund, Sweden

关键词: Platelets;    Toxins;    Hemolytic-uremic syndrome;    Blood;    Endothelial cells;    White blood cells;    Flow cytometry;    Protein synthesis;   

DOI  :  10.1371/journal.ppat.1004619

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Shiga toxin (Stx) is the main virulence factor of enterohemorrhagic Escherichia coli, which are non-invasive strains that can lead to hemolytic uremic syndrome (HUS), associated with renal failure and death. Although bacteremia does not occur, bacterial virulence factors gain access to the circulation and are thereafter presumed to cause target organ damage. Stx was previously shown to circulate bound to blood cells but the mechanism by which it would potentially transfer to target organ cells has not been elucidated. Here we show that blood cell-derived microvesicles, shed during HUS, contain Stx and are found within patient renal cortical cells. The finding was reproduced in mice infected with Stx-producing Escherichia coli exhibiting Stx-containing blood cell-derived microvesicles in the circulation that reached the kidney where they were transferred into glomerular and peritubular capillary endothelial cells and further through their basement membranes followed by podocytes and tubular epithelial cells, respectively. In vitro studies demonstrated that blood cell-derived microvesicles containing Stx undergo endocytosis in glomerular endothelial cells leading to cell death secondary to inhibited protein synthesis. This study demonstrates a novel virulence mechanism whereby bacterial toxin is transferred within host blood cell-derived microvesicles in which it may evade the host immune system.

【 授权许可】

CC BY