Human Platelets Attenuate<i>Aspergillus</i>Species via Granule‐Dependent Mechanisms

Perkhofer, Susanne; Kehrel, Beate E.; Dierich, Manfred P.; Donnelly, J. Peter; Nußbaumer, Walter; Hofmann, Johann; Eiff, Christof von; Lass‐Flörl, Cornelia

doi:10.1086/591458

Cited by 65 publications

(70 citation statements)

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“…Previous evidence was obtained for an interaction between platelets and the cell wall of C. albicans but the triggering molecules of this pathogenic yeast were not identified (29,33). During invasive fungal infection, C. albicans-derived cell wall components, including ␤-1,3 glucans, are known to circulate in patients' sera.…”

Section: Discussionmentioning

confidence: 99%

“…act with platelets in circulating blood (33). This interaction between the fungus and the host occurs at the level of the cell wall, which consists mainly of polysaccharides associated with proteins and lipids (17).…”

mentioning

confidence: 99%

“…C. albicans infections continue to be a serious clinical problem with respect to increased morbidity and mortality (36). The cell wall components of C. albicans can interfere with platelets in circulating blood and contribute to the adherence of C. albicans to fibrin-platelet matrices (29,33). Platelets also interact with the yeast form and hyphae of C. albicans (50).…”

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confidence: 99%

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

Vancraeyneste

Charlet

Guérardel

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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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.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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

Vancraeyneste

Charlet

Guérardel

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…Platelets bind plasma-opsonized hyphae and degranulate (42). The interaction of platelets with hyphae results in reduced hyphal galactomannan release, impaired hyphal elongation, and loss of hyphal wall integrity, and these effects were inhibited when granule exocytosis was blocked (42,123). Serotonin, a component of platelet granules, has also been found to kill both conidia and hyphae and to induce damage to fungal cell membranes (88,124).…”

Section: Plateletsmentioning

confidence: 99%

Innate Immunity toAspergillusSpecies

Park¹,

2009

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SUMMARY All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused by Aspergillus species, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses to Aspergillus species is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses against Aspergillus species that dictate the outcome of this host-microbe interaction.

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“…Furthermore, it has been reported that liver transplant recipients with thrombocytopenia have a considerably higher incidence of fungal infection than nonthrombocytopenic patients (3). There are some reports on the interaction between A. fumigatus and platelets, showing inhibition of fungal growth potentially involving the release of known plateletderived microbial peptides, as well as direct physical interaction between platelets and conidia or hyphae (4,16).…”

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Activation of Platelets byAspergillus fumigatusand Potential Role of Platelets in the Immunopathogenesis of Aspergillosis

Rødland

Ueland

Pedersen³

et al. 2010

Infect Immun

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Aspergillus fumigatus is the most frequent cause of invasive mold infections worldwide. Platelets contribute to inflammation and promote thrombosis, characteristically seen in aspergillosis, and might be involved both in antifungal defense and in the histopathological process. In the experiments reported here, in vitro activation of platelets by conidia, swollen conidia, and hyphae from A. fumigatus was assessed by flow cytometry and enzyme immunoassays. THP-1 monocytes and human monocytes with and without platelets were cultured with hyphae from A. fumigatus, and the release of interleukin-8 (IL-8) was measured by enzyme immunoassays. A. fumigatus potently induced the expression of CD62-p and CD63 and the release of CD40 ligand, RANTES, and Dickkopf homolog 1 in platelets, with particularly enhancing effects of hyphae compared with conidia. The hypha-mediated activation of platelets further enhanced the release of IL-8 both in THP-1 monocytes and in human adherent monocytes. In conclusion, we have found that A. fumigatus is a potent inducer of platelet-mediated inflammation, potentially promoting protective as well as harmful responses during aspergillosis.Aspergillosis is the most common mold infection worldwide, and Aspergillus fumigatus accounts for more than 90% of the cases (6). In contrast to most human pathogens, which are encountered infrequently, A. fumigatus spores are inhaled on a daily basis, and occasionally, exposure to large numbers of conidia can occur. The first-line host defense against Aspergillus infection is based on innate immunity mediated by monocytes/macrophages and neutrophils (11,12,17,18). The adaptive immune system responds to a pathogen only after it has been recognized by the innate immune system (11). While inadequate immune responses may predispose to invasive disease, overly robust responses can result in immune-mediated inflammatory tissue damage. Thus, imbalanced immune responses to A. fumigatus may result in a spectrum of human disease states ranging from allergic bronchopulmonary aspergillosis to invasive aspergillosis in the immunocompromised host (9). Despite better diagnostic tools and therapeutic advances, the infection is difficult to diagnose and treat, and the outcome of invasive aspergillosis is often fatal.Several lines of evidence support a role for platelets in inflammation (10). Platelet-mediated inflammation has been demonstrated during various acute and chronic infections, and it has been suggested that platelets contribute to antimicrobial defenses (5, 8). Very little is known about the role of platelets in defense against Aspergillus infection. In this connection, it is interesting that important risk groups for invasive aspergillosis, e.g., patients with chemotherapy-induced neutropenia and recipients of hematopoietic stem cell transplants (6, 13), very often have concurrent thrombocytopenia in addition to neutropenia. Furthermore, it has been reported that liver transplant recipients with thrombocytopenia have a considerably higher incidence of fungal infe...

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Human Platelets AttenuateAspergillusSpecies via Granule‐Dependent Mechanisms

Cited by 65 publications

References 13 publications

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

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

Innate Immunity toAspergillusSpecies

Activation of Platelets byAspergillus fumigatusand Potential Role of Platelets in the Immunopathogenesis of Aspergillosis

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