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Annexin induces cellular uptake of extracellular vesicles and delays disease in Escherichia coli O157:H7 infection

Tontanahal, Ashmita LU ; Arvidsson, Ida LU and Karpman, Diana LU orcid (2021) In Microorganisms 9(6).
Abstract

Enterohemorrhagic Escherichia coli secrete Shiga toxin and lead to hemolytic uremic syn-drome. Patients have high levels of circulating prothrombotic extracellular vesicles (EVs) that expose phosphatidylserine and tissue factor and transfer Shiga toxin from the circulation into the kidney. Annexin A5 (AnxA5) binds to phosphatidylserine, affecting membrane dynamics. This study investi-gated the effect of anxA5 on EV uptake by human and murine phagocytes and used a mouse model of EHEC infection to study the effect of anxA5 on disease and systemic EV levels. EVs derived from human whole blood or HeLa cells were more readily taken up by THP-1 cells or RAW264.7 cells when the EVs were coated with anxA5. EVs from HeLa cells incubated with... (More)

Enterohemorrhagic Escherichia coli secrete Shiga toxin and lead to hemolytic uremic syn-drome. Patients have high levels of circulating prothrombotic extracellular vesicles (EVs) that expose phosphatidylserine and tissue factor and transfer Shiga toxin from the circulation into the kidney. Annexin A5 (AnxA5) binds to phosphatidylserine, affecting membrane dynamics. This study investi-gated the effect of anxA5 on EV uptake by human and murine phagocytes and used a mouse model of EHEC infection to study the effect of anxA5 on disease and systemic EV levels. EVs derived from human whole blood or HeLa cells were more readily taken up by THP-1 cells or RAW264.7 cells when the EVs were coated with anxA5. EVs from HeLa cells incubated with RAW264.7 cells induced phosphatidylserine exposure on the cells, suggesting a mechanism by which anxA5-coated EVs can bind to phagocytes before uptake. Mice treated with anxA5 for six days after inoculation with E. coli O157:H7 showed a dose-dependent delay in the development of clinical disease. Treated mice had lower levels of EVs in the circulation. In the presence of anxA5, EVs are taken up by phagocytes and their systemic levels are lower, and, as EVs transfer Shiga toxin to the kidney, this could postpone disease development.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Annexin A5, Enterohemorrhagic Escherichia coli, Extracellular vesicles, Hemolytic uremic syndrome, Phagocytes, Shiga toxin
in
Microorganisms
volume
9
issue
6
article number
1143
publisher
MDPI AG
external identifiers
  • scopus:85106427031
  • pmid:34073384
ISSN
2076-2607
DOI
10.3390/microorganisms9061143
language
English
LU publication?
yes
id
f9220bf9-22d1-4fcb-bc26-13eb0e82b764
date added to LUP
2021-06-11 12:28:26
date last changed
2024-06-15 12:25:32
@article{f9220bf9-22d1-4fcb-bc26-13eb0e82b764,
  abstract     = {{<p>Enterohemorrhagic Escherichia coli secrete Shiga toxin and lead to hemolytic uremic syn-drome. Patients have high levels of circulating prothrombotic extracellular vesicles (EVs) that expose phosphatidylserine and tissue factor and transfer Shiga toxin from the circulation into the kidney. Annexin A5 (AnxA5) binds to phosphatidylserine, affecting membrane dynamics. This study investi-gated the effect of anxA5 on EV uptake by human and murine phagocytes and used a mouse model of EHEC infection to study the effect of anxA5 on disease and systemic EV levels. EVs derived from human whole blood or HeLa cells were more readily taken up by THP-1 cells or RAW264.7 cells when the EVs were coated with anxA5. EVs from HeLa cells incubated with RAW264.7 cells induced phosphatidylserine exposure on the cells, suggesting a mechanism by which anxA5-coated EVs can bind to phagocytes before uptake. Mice treated with anxA5 for six days after inoculation with E. coli O157:H7 showed a dose-dependent delay in the development of clinical disease. Treated mice had lower levels of EVs in the circulation. In the presence of anxA5, EVs are taken up by phagocytes and their systemic levels are lower, and, as EVs transfer Shiga toxin to the kidney, this could postpone disease development.</p>}},
  author       = {{Tontanahal, Ashmita and Arvidsson, Ida and Karpman, Diana}},
  issn         = {{2076-2607}},
  keywords     = {{Annexin A5; Enterohemorrhagic Escherichia coli; Extracellular vesicles; Hemolytic uremic syndrome; Phagocytes; Shiga toxin}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  publisher    = {{MDPI AG}},
  series       = {{Microorganisms}},
  title        = {{Annexin induces cellular uptake of extracellular vesicles and delays disease in Escherichia coli O157:H7 infection}},
  url          = {{http://dx.doi.org/10.3390/microorganisms9061143}},
  doi          = {{10.3390/microorganisms9061143}},
  volume       = {{9}},
  year         = {{2021}},
}