Short fungal fractions of β-1,3 glucans affect platelet activation

Abstract

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 ␤-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 ␤-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 mol/l) reduced ATP release and prevented the phosphorylation of protein kinase C. BGFs diminished the expression of P-selectin and the activation of ␣ IIb␤3. BGFs decreased platelet aggregation and the interaction between thrombin-stimulated platelets and neutrophils, fibrinogen, and C. albicans. GLc5 decreased ATP release and TGF-␤1 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.

Stepping Up to the Plate(let) against Candida albicans

“…While C. albicans was shown previously to affect platelet aggregation (33,34), the mechanisms behind this inhibition have not been clearly elucidated. One study attributes this inhibition to the release of the metabolite gliotoxin (33).…”

A decrease in anaerobic bacteria promotes Candida glabrata overgrowth while β-glucan treatment restores the gut microbiota and attenuates colitis

“…The first point of contact between C. glabrata and its host is the fungal cell wall, whose major constituent is β-glucan. The biological activity of β-glucans is related to their molecular structure, including their solubility, their degree of branching, and their effect on the inhibition or activation of host pattern recognition receptors [ 13 ]. This study used soluble short fractions of β-glucans, purified from C. glabrata in a DSS-induced colitis model.…”

“…The anti-inflammatory activities of β-glucans from fungi have been emphasized in different studies, which have shown that soluble β-glucans can activate or block different receptors such as CD11b/CD18, dectin-1, or TLR-4 [ 11 , 27 ]. Recently, short fractions of β-glucans were shown to block the activation of platelets mediated by TLR-4 expression [ 13 ]. β-glucans can initiate the innate immune response and then trigger effective immune responses including phagocytosis and cytokine production that lead to fungal elimination.…”

“…The nature and purity of the soluble β-glucan fractions are then confirmed by mass spectrometry and NMR analyses. The concentration of β-glucan fractions is measured using sulfuric acid and phenol (5%) in 96-well plates [ 9 , 13 ].…”

“…β-glucans can directly activate leukocytes, and further stimulate their phagocytic, cytotoxic, and antimicrobial activities. β-glucans are recognized by several receptors, in particular integrin α M β 2 , dectin-1 and TLR-4, thereby triggering an immune response [ 11 – 13 ].…”