Babesia divergens glycosylphosphatidylinositols modulate blood coagulation and induce Th2-biased cytokine profiles in antigen presenting cells.
Animals
Antigens, Protozoan
/ immunology
Apoptosis
/ immunology
Babesia
/ immunology
Babesiosis
/ blood
Blood Coagulation
Cytokines
/ immunology
Dendritic Cells
/ immunology
Glycosylphosphatidylinositols
/ immunology
Macrophages
/ immunology
Major Histocompatibility Complex
/ immunology
Mice
Rats
Rats, Wistar
Antigen presentation
Coagulation
Glycosylphosphatidylinositol
Interleukin
Major histocompatibility complex
Journal
Biochimie
ISSN: 1638-6183
Titre abrégé: Biochimie
Pays: France
ID NLM: 1264604
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
received:
02
01
2019
accepted:
29
01
2019
pubmed:
5
10
2019
medline:
7
1
2020
entrez:
5
10
2019
Statut:
ppublish
Résumé
Glycosylphosphatidylinositols (GPIs) are glycolipids described as toxins of protozoan parasites due to their inflammatory properties in mammalian hosts characterized by the production of interleukin (IL)-1, IL-12 and tumor necrosis factor (TNF)-α. In the present work, we studied the cytokines produced by antigen presenting cells in response to ten different GPI species extracted from Babesia divergens, responsible for babesiosis. Interestingly, B. divergens GPIs induced the production of anti-inflammatory cytokines (IL-2, IL-5) and of the regulatory cytokine IL-10 by macrophages and dendritic cells. In contrast to all protozoan GPIs studied until now, GPIs from B. divergens did not stimulate the production of TNF-α and IL-12, leading to a unique Th1/Th2 profile. Analysis of the carbohydrate composition of the B. divergens GPIs indicated that the di-mannose structure was different from the evolutionary conserved tri-mannose structure, which might explain the particular cytokine profile they induce. Expression of major histocompatibility complex (MHC) molecules on dendritic cells and apoptosis of mouse peritoneal cells were also analysed. B. divergens GPIs did not change expression of MHC class I, but decreased expression of MHC class II at the cell surface, while GPIs slightly increased the percentages of apoptotic cells. During pathogenesis of babesiosis, the inflammation-coagulation auto-amplification loop can lead to thrombosis and the effect of GPIs on coagulation parameters was investigated. Incubation of B. divergens GPIs with rat plasma ex vivo led to increase of fibrinogen levels and to prolonged activated partial thromboplastin time, suggesting a direct modulation of the extrinsic coagulation pathway by GPIs.
Identifiants
pubmed: 31585151
pii: S0300-9084(19)30265-2
doi: 10.1016/j.biochi.2019.09.007
pmc: PMC7079338
pii:
doi:
Substances chimiques
Antigens, Protozoan
0
Cytokines
0
Glycosylphosphatidylinositols
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
135-144Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.
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