Short fungal fractions of β-1,3 glucans affect platelet activation.
Platelets are capable of binding, aggregating, and internalizing microorganisms, which enhances the elimination of pathogens from the blood. The yeast Candida albicans is a pathobiont causing life-threatening invasive infections. Its cell wall contains β-1,3 glucans that are known to trigger a wide range of host cell activities and to circulate during infection. We studied the effect of β-1,3 glucan fractions (BGFs) consisting of diglucosides (Glc2), tetraglucosides (Glc4), and pentaglucosides (Glc5) on human platelets, their mechanisms of action, and their possible impact on host defenses. The effect of BGFs on the coagulation process was determined by measuring thrombin generation. Platelets pretreated with BGFs were analyzed in terms of activation, receptor expression, aggregation, and adhesion to neutrophils and to C. albicans The results show that BGFs affected the endogenous thrombin potential in a concentration-dependent manner. For platelet activation, BGFs at a low concentration (2 μmol/l) reduced ATP release and prevented the phosphorylation of protein kinase C. BGFs diminished the expression of P-selectin and the activation of αIIbβ3 BGFs decreased platelet aggregation and the interaction between thrombin-stimulated platelets and neutrophils, fibrinogen, and C. albicans GLc5 decreased ATP release and TGF-β1 production in response to TLR4 upregulation in thrombin-stimulated platelets, but TLR4 blockage abolished the effect of BGFs on platelets. This study provides evidence that fungal pentaglucosides modulate platelet activity mediated via TLR4 stimulation and reduce platelet-neutrophil interaction.
Univ Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; CHRU Lille, Lille, France;
Hélène
H
Vancraeyneste
Univ Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; CHRU Lille, Lille, France;
Rogatien
R
Charlet
Université de Lille 1, Unité de Glycobiologie Structurale et Fonctionnelle, UGSF, Villeneuve d'Ascq, France; CNRS, UMR 8576, Villeneuve d'Ascq, France;
Yann
Y
Guerardel
Univ Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; CHRU Lille, Lille, France;
Laura
L
Choteau
Laboratoire d'Hémostase, Pôle de Pathologie Génétique, Lille, France;
Anne
A
Bauters
Plateforme d'Interaction Moléculaire, IMPRT-IFR114, Faculté de Médecine de Lille, Lille, France;
Meryem
M
Tardivel
Service de Parasitologie Mycologie, Pole de Biologie Pathologie Génétique, Lille, France; and.
Nadine
N
François
Univ Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; CHRU Lille, Lille, France;
Laurent
L
Dubuquoy
Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic, Cleveland, Ohio.
Dmitry
D
Soloviev
Univ Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; CHRU Lille, Lille, France; Service de Parasitologie Mycologie, Pole de Biologie Pathologie Génétique, Lille, France; and.
Daniel
D
Poulain
Univ Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; CHRU Lille, Lille, France; Service de Parasitologie Mycologie, Pole de Biologie Pathologie Génétique, Lille, France; and.
Boualem
B
Sendid
Univ Lille Nord de France, Lille, France; UDSL, Lille, France; INSERM U995, Lille, France; CHRU Lille, Lille, France; samir.jawhara-3@univ-lille2.fr.
Samir
0000-0002-2759-975X
S
Jawhara
D000255:Adenosine Triphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002176:Candida albicans; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D005658:Fungi / Q000737:chemistry; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils; D019007:P-Selectin / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D047071:beta-Glucans / Q000494:pharmacology*
D005960:Glucosides; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C546937:SELP protein, human; C508960:TGFB1 protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D047071:beta-Glucans; D000255:Adenosine Triphosphate; D005340:Fibrinogen; D011493:Protein Kinase C; D013917:Thrombin
Candida albicans; aggregation; coagulation; platelets; toll-like receptors; β-glucans