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Thromb Haemost 2014; 112(04): 632-639
DOI: 10.1160/TH14-01-0074
Theme Issue Article
Schattauer GmbH

Platelet immunology in fungal infections

Cornelia Speth
1   Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria
,
Günter Rambach
1   Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria
,
Cornelia Lass-Flörl
1   Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria
› Author Affiliations
Further Information

Publication History

Received: 24 January 2014

Accepted after major revision: 30 May 2014

Publication Date:
20 November 2017 (online)

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Summary

Up to date, perception of platelets has changed from key players in coagulation to multitaskers within the immune network, connecting its most diverse elements and crucially shaping their interplay with invading pathogens such as fungi. In addition, antimicrobial effector molecules and mechanisms in platelets enable a direct inhibitory effect on fungi, thus completing their immune capacity. To precisely assess the impact of platelets on the course of invasive fungal infections is complicated by some critical parameters. First, there is a fragile balance between protective antimicrobial effects and detrimental reactions that aggravate the fungal pathogenesis. Second, some platelet effects are exerted indirectly by other immune mediators and are thus difficult to quantify. Third, drugs such as antimycotics, antibiotics, or cytostatics, are commonly administered to the patients and might modulate the interplay between platelets and fungi. Our article highlights selected aspects of the complex interactions between platelets and fungi and the relevance of these processes for the pathogenesis of fungal infections.

Keywords

Platelets - fungi - invasive infection - innate immunity
 

  • References

  • 1 Semple JW, Italiano Jr., JE, Freedman J. Platelets and the immune continuum. Nat Rev Immunol 2011; 11: 264-274.
    CrossrefPubMedGoogle Scholar
  • 2 Coppinger JA, Maguire PB. Insights into the platelet releasate. Curr Pharm Des 2007; 13: 2640-2646.
    CrossrefPubMedGoogle Scholar
  • 3 Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost 2011; 105 (Suppl. 01) S13-S33.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Speth C, Loffler J, Krappmann S. et al. Platelets as immune cells in infectious diseases. Future Microbiol 2013; 8: 1431-1451.
    CrossrefPubMedGoogle Scholar
  • 5 Garraud O, Cognasse F. Platelet Toll-like receptor expression: the link between “danger” ligands and inflammation. Inflamm Allergy Drug Targets 2010; 9: 322-333.
    CrossrefPubMedGoogle Scholar
  • 6 Semple JW, Freedman J. Platelets and innate immunity. Cell Mol Life Sci 2010; 67: 499-511.
    CrossrefPubMedGoogle Scholar
  • 7 Tapping RI. Innate immune sensing and activation of cell surface Toll-like receptors. Semin Immunol 2009; 21: 175-184.
    CrossrefPubMedGoogle Scholar
  • 8 Shiraki R, Inoue N, Kawasaki S. et al. Expression of Toll-like receptors on human platelets. Thromb Res 2004; 113: 379-385.
    CrossrefPubMedGoogle Scholar
  • 9 Krijgsveld J, Zaat SA, Meeldijk J. et al. Thrombocidins, mirobiocidal proteins from human blood platelets, are C-terminal deletion products of CXC chemokines. J Biol Chem 2000; 275: 20374-20381.
    CrossrefPubMedGoogle Scholar
  • 10 Yount NY, Yeaman MR. Peptide antimicrobials: cell wall as a bacterial target. Ann NY Acad Sci 2013; 1277: 127-138.
    CrossrefPubMedGoogle Scholar
  • 11 Youssefian T, Drouin A, Masse JM. et al. Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood 2002; 99: 4021-4029.
    CrossrefPubMedGoogle Scholar
  • 12 Czapiga M, Kirk AD, Lekstrom-Himes J. Platelets deliver costimulatory signals to antigen-presenting cells: a potential bridge between injury and immune activation. Exp Hematol 2004; 32: 135-139.
    CrossrefPubMedGoogle Scholar
  • 13 Gerdes N, Zhu L, Ersoy M. et al. Platelets regulate CD4(+) T-cell differentiation via multiple chemokines in humans. Thromb Haemost 2011; 106: 353-362.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Kasper B, Brandt E, Brandau S. et al. Platelet factor 4 (CXC chemokine ligand 4) differentially regulates respiratory burst, survival, and cytokine expression of human monocytes by using distinct signaling pathways. J Immunol 2007; 179: 2584-2591.
    CrossrefPubMedGoogle Scholar
  • 15 Maugeri N, Rovere-Querini P, Evangelista V. et al. Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and {beta}2 integrin-dependent cell clearance program. Blood 2009; 113: 5254-5265.
    CrossrefPubMedGoogle Scholar
  • 16 Sprague DL, Elzey BD, Crist SA. et al. Platelet-mediated modulation of adaptive immunity: unique delivery of CD154 signal by platelet-derived membrane vesicles. Blood 2008; 111: 5028-5036.
    CrossrefPubMedGoogle Scholar
  • 17 Weyrich AS, Zimmerman GA. Platelets: signaling cells in the immune continuum. Trends Immunol 2004; 25: 489-495.
    CrossrefPubMedGoogle Scholar
  • 18 Vieira-de-Abreu A, Campbell RA, Weyrich AS. et al. Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum. Semin Immunopathol 2012; 34: 5-30.
    CrossrefPubMedGoogle Scholar
  • 19 Scheuerer B, Ernst M, Durrbaum-Landmann I. et al. The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages. Blood 2000; 95: 1158-1166.
    PubMedGoogle Scholar
  • 20 Scull CM, Hays WD, Fischer TH. Macrophage pro-inflammatory cytokine secretion is enhanced following interaction with autologous platelets. J Inflamm 2010; 7: 53.
    CrossrefPubMedGoogle Scholar
  • 21 Cognasse F, Hamzeh-Cognasse H, Lafarge S. et al. Human platelets can activate peripheral blood B cells and increase production of immunoglobulins. Exp Hematol 2007; 35: 1376-1387.
    CrossrefPubMedGoogle Scholar
  • 22 Hamzeh-Cognasse H, Cognasse F, Palle S. et al. Direct contact of platelets and their released products exert different effects on human dendritic cell maturation. BMC Immunol 2008; 9: 54.
    CrossrefPubMedGoogle Scholar
  • 23 Lass-Flörl C. The changing face of epidemiology of invasive fungal diseases in Europe. Mycoses 2009; 52: 197-205.
    CrossrefPubMedGoogle Scholar
  • 24 Rambach G, Speth C, Lass-Flörl C. Changing epidemiology of invasive fungal infections in critically ill patients in the intensive care unit. J Invas Fungal Infect 2010; 3: 116-122.
    PubMedGoogle Scholar
  • 25 Guimaraes MD, Marchiori E, de Souza Portes MG. et al. Fungal infection mimicking pulmonary malignancy: clinical and radiological characteristics. Lung 2013; 191: 655-662.
    CrossrefPubMedGoogle Scholar
  • 26 Cadelis G. [Hemoptysis complicating bronchopulmonary mucormycosis in a diabetic patient]. Rev Pneumol Clin 2013; 69: 83-88.
    CrossrefPubMedGoogle Scholar
  • 27 Guazzelli LS, Severo CB, Hoff LS. et al. Aspergillus fumigatus fungus ball in the pleural cavity. J Bras Pneumol 2012; 38: 125-132.
    CrossrefPubMedGoogle Scholar
  • 28 Kamai Y, Chiang LY, Lopes Bezerra LM. et al. Interactions of Aspergillus fumigatus with vascular endothelial cells. Med Mycol 2006; 44 (Suppl. 01) S115-S117.
    CrossrefPubMedGoogle Scholar
  • 29 Delaloye J, Calandra T. Invasive candidiasis as a cause of sepsis in the critically ill patient. Virulence 2014; 5: 161-169.
    CrossrefPubMedGoogle Scholar
  • 30 van de Veerdonk FL, Kullberg BJ, Netea MG. Pathogenesis of invasive candidiasis. Curr Opin Crit Care 2010; 16: 453-459.
    CrossrefPubMedGoogle Scholar
  • 31 Attigah N, Herpel E, Kotelis D. et al. Endovascular repair of aspergilloma-induced arrosion bleeding of the subclavian artery. Chirurg 2008; 79: 984-987.
    CrossrefPubMedGoogle Scholar
  • 32 Sorgo AG, Heilmann CJ, Brul S. et al. Beyond the wall: Candida albicans secret(e)s to survive. FEMS Microbiol Lett 2013; 338: 10-17.
    CrossrefPubMedGoogle Scholar
  • 33 Girard V, Dieryckx C, Job C. et al. Secretomes: the fungal strike force. Proteomics 2013; 13: 597-608.
    CrossrefPubMedGoogle Scholar
  • 34 Fontaine T, Delangle A, Simenel C. et al. Galactosaminogalactan, a new immunosuppressive polysaccharide of Aspergillus fumigatus. Plos Pathog 2011; 7: e1002372.
    CrossrefPubMedGoogle Scholar
  • 35 Barnes PD, Marr KA. Risks, diagnosis and outcomes of invasive fungal infections in haematopoietic stem cell transplant recipients. Br J Haematol 2007; 139: 519-531.
    CrossrefPubMedGoogle Scholar
  • 36 Hsu JL, Ruoss SJ, Bower ND. et al. Diagnosing invasive fungal disease in critically ill patients. Crit Rev Microbiol 2011; 37: 277-312.
    CrossrefPubMedGoogle Scholar
  • 37 Roeder A, Kirschning CJ, Rupec RA. et al. Toll-like receptors and innate anti-fungal responses. Trends Microbiol 2004; 12: 44-49.
    CrossrefPubMedGoogle Scholar
  • 38 Bertling A, Niemann S, Uekotter A. et al. Candida albicans and its metabolite gliotoxin inhibit platelet function via interaction with thiols. Thromb Haemost 2010; 104: 270-278.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Lass-Flörl C, Wiedauer B, Mayr A. et al. Antifungal properties of 5-HT (serotonin) against Aspergillus spp. in vitro. Int J Med Microbiol 2005; 26: 335-337.
    PubMedGoogle Scholar
  • 40 Flaujac C, Boukour S, Cramer-Borde E. Platelets and viruses: an ambivalent relationship. Cell Mol Life Sci 2010; 67: 545-556.
    CrossrefPubMedGoogle Scholar
  • 41 Stone D, Liu Y, Shayakhmetov D. et al. Adenovirus-platelet interaction in blood causes virus sequestration to the reticuloendothelial system of the liver. J Virol 2007; 81: 4866-4871.
    CrossrefPubMedGoogle Scholar
  • 42 Denning DW. Invasive aspergillosis. Clin Infect Dis 1998; 26: 781-803.
    CrossrefPubMedGoogle Scholar
  • 43 Kullberg BJ, Lashof AML. Epidemiology of opportunistic invasive mycoses. Eur J Med Res 2002; 7: 183-191.
    PubMedGoogle Scholar
  • 44 Christin L, Wysong DR, Meshulam T. et al. Human platelets damage Aspergillus fumigatus hyphae and may supplement killing by neutrophils. Infect Immun 1998; 66: 1181-1189.
    PubMedGoogle Scholar
  • 45 Rodland EK, Ueland T, Pedersen TM. et al. Activation of platelets by Aspergillus fumigatus and potential role of platelets in the immunopathogenesis of Aspergillosis. Infect Immun 2010; 78: 1269-1275.
    CrossrefPubMedGoogle Scholar
  • 46 Perkhofer S, Kehrel BE, Dierich MP. et al. Human platelets attenuate Aspergillus species via granule-dependent mechanisms. J Infect Dis 2008; 198: 1243-1246.
    CrossrefPubMedGoogle Scholar
  • 47 Speth C, Hagleitner M, Ott HW. et al. Aspergillus fumigatus Activates Thrombocytes by Secretion of Soluble Compounds. J Infect Dis 2013; 207: 823-833.
    CrossrefPubMedGoogle Scholar
  • 48 Nouer SA, Nucci M, Kumar NS. et al. Baseline platelet count and creatinine clearance rate predict the outcome of neutropenia-related invasive aspergillosis. Clin Infect Dis 2012; 54: e173-e183.
    CrossrefPubMedGoogle Scholar
  • 49 Speth C, Blum G, Hagleitner M. et al. Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility. Med Microbiol Immunol 2013; 202: 379-389.
    CrossrefPubMedGoogle Scholar
  • 50 Rambach G, Oberhauser H, Speth C. et al. Susceptibility of Candida species and various moulds to antimycotic drugs: use of epidemiological cutoff values according to EUCAST and CLSI in an 8-year survey. Med Mycol 2011; 49: 856-863.
    CrossrefPubMedGoogle Scholar
  • 51 Maisch PA, Calderone RA. Adherence of Candida albicans to a fibrin-platelet matrix formed in vitro. Infect Immun 1980; 27: 650-656.
    PubMedGoogle Scholar
  • 52 Robert R, Mahaza C, Miegeville M. et al. Binding of resting platelets to Candida albicans germ tubes. Infect Immun 1996; 64: 3752-3757.
    PubMedGoogle Scholar
  • 53 Robert R, Nail S, Marot-Leblond A. et al. Adherence of platelets to Candida species in vivo. Infect Immun 2000; 68: 570-576.
    CrossrefPubMedGoogle Scholar
  • 54 Willcox M, Webb B, Thakur A. et al. Interactions between Candida species and platelets. J Med Microbiol 1998; 47: 103-110.
    CrossrefPubMedGoogle Scholar
  • 55 Woth G, Tokes-Fuzesi M, Magyarlaki T. et al. Activated platelet-derived micro-particle numbers are elevated in patients with severe fungal (Candida albicans) sepsis. Ann Clin Biochem 2012; 49: 554-560.
    CrossrefPubMedGoogle Scholar
  • 56 Carvalho Neiva TJ, dos Santos JI. Effect of pathogenic yeasts on human platelet aggregation. Braz J Infect Dis 2003; 7: 370-374.
    PubMedGoogle Scholar
  • 57 Drago L, Bortolin M, Vassena C. et al. Antimicrobial activity of pure platelet-rich plasma against microorganisms isolated from oral cavity. BMC Microbiol 2013; 13: 47.
    CrossrefPubMedGoogle Scholar
  • 58 Kwakman PH, Krijgsveld J, de BL. et al. Native thrombocidin-1 and unfolded thrombocidin-1 exert antimicrobial activity via distinct structural elements. J Biol Chem 2011; 286: 43506-43514.
    CrossrefPubMedGoogle Scholar
  • 59 Tang Y, Yeaman M, Selsted ME. Antimicrobial peptides from human platelets. Infect Immun 2002; 70: 6524-6533.
    CrossrefPubMedGoogle Scholar
  • 60 Petrikkos G, Skiada A, Lortholary O. et al. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis 2012; 54 (Suppl. 01) S23-S34.
    CrossrefPubMedGoogle Scholar
  • 61 Perkhofer S, Kainzner B, Kehrel BE. et al. Potential antifungal effects of human platelets against zygomycetes in vitro. J Infect Dis 2009; 200: 1176-1179.
    CrossrefPubMedGoogle Scholar
  • 62 Hamilos G, Samonis G, Kontoyiannis DP. Pulmonary mucormycosis. Semin Respir Crit Care Med 2011; 32: 693-702.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 63 Nail S, Robert R, Dromer F. et al. Susceptibilities of Cryptococcus neoformans strains to platelet binding in vivo and to the fungicidal activity of thrombin-induced platelet microbicidal proteins in vitro. Infect Immun 2001; 69: 1221-1225.
    CrossrefPubMedGoogle Scholar
  • 64 Rambach G, Wurzner R, Speth C. Complement: an efficient sword of innate immunity. Contrib Microbiol 2008; 15: 78-100.
    PubMedGoogle Scholar
  • 65 Speth C, Rambach G. Complement Attack against Aspergillus and Corresponding Evasion Mechanisms. Interdiscip Perspect Infect Dis 2012; 2012: 463794.
    PubMedGoogle Scholar
  • 66 Speth C, Prodinger W, Würzner R. et al. Complement. In: Fundamental Immunology. 6th ed.. Philadelphia, USA: Lippincott Williams & Wilkins; 2008. pp. 1047-1078.
    Google Scholar
  • 67 Del Conde I, Cruz MA, Zhang H. et al. Platelet activation leads to activation and propagation of the complement system. J Exp Med 2005; 201: 871-879.
    CrossrefPubMedGoogle Scholar
  • 68 Peerschke EI, Yin W, Grigg SE. et al. Blood platelets activate the classical pathway of human complement. J Thromb Haemost 2006; 4: 2035-2042.
    CrossrefPubMedGoogle Scholar
  • 69 Hamad OA, Ekdahl KN, Nilsson PH. et al. Complement activation triggered by chondroitin sulfate released by thrombin receptor-activated platelets. J Thromb Haemost 2008; 6: 1413-1421.
    CrossrefPubMedGoogle Scholar
  • 70 Hamad OA, Nilsson PH, Lasaosa M. et al. Contribution of chondroitin sulfate A to the binding of complement proteins to activated platelets. PLoS One 2010; 5: e12889.
    CrossrefPubMedGoogle Scholar
  • 71 Peerschke EI, Andemariam B, Yin W. et al. Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura. Br J Haematol 2010; 148: 638-645.
    CrossrefPubMedGoogle Scholar
  • 72 Peerschke EI, Yin W, Alpert DR. et al. Serum complement activation on heterologous platelets is associated with arterial thrombosis in patients with systemic lupus erythematosus and antiphospholipid antibodies. Lupus 2009; 18: 530-538.
    CrossrefPubMedGoogle Scholar
  • 73 Peerschke EI, Yin W, Ghebrehiwet B. Complement activation on platelets: implications for vascular inflammation and thrombosis. Mol Immunol 2010; 47: 2170-2175.
    CrossrefPubMedGoogle Scholar
  • 74 Langeggen H, Berge KE, Johnson E. et al. Human umbilical vein endothelial cells express complement receptor 1 (CD35) and complement receptor 4 (CD11c/CD18) in vitro. Inflammation 2002; 26: 103-110.
    CrossrefPubMedGoogle Scholar
  • 75 Skeie JM, Fingert JH, Russell SR. et al. Complement component C5a activates ICAM-1 expression on human choroidal endothelial cells. Invest Ophthalmol Vis Sci 2010; 51: 5336-5342.
    CrossrefPubMedGoogle Scholar
  • 76 Ikeda K, Nagasawa K, Horiuchi T. et al. C5a induces tissue factor activity on endothelial cells. Thromb Haemost 1997; 77: 394-398.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 77 Ward PA. The harmful role of c5a on innate immunity in sepsis. J Innate Immun 2010; 2: 439-445.
    CrossrefPubMedGoogle Scholar
  • 78 Wiedmer T, Esmon CT, Sims PJ. Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase. Blood 1986; 68: 875-880.
    PubMedGoogle Scholar
  • 79 Verschoor A, Langer HF. Crosstalk between platelets and the complement system in immune protection and disease. Thromb Haemost 2013; 110: 910-919.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 80 Yeaman M, Sullam P, Dazin P. et al. Fluconazole and platelet microbicidal protein inhibit Candida adherence to platelets in vitro. Antimicrob Agents Chemother 1994; 38: 1460-1465.
    CrossrefPubMedGoogle Scholar
  • 81 Yeaman MR, Cheng D, Desai B. et al. Susceptibility to thrombin-induced platelet microbicidal protein is associated with increased fluconazole efficacy against experimental endocarditis due to Candida albicans. Antimicrob Agents Chemother 2004; 48: 3051-3056.
    CrossrefPubMedGoogle Scholar
  • 82 Perkhofer S, Striessnig B, Sartori B. et al. Interaction of platelets and anidulafungin against Aspergillus fumigatus. Antimicrob Agents Chemother 2013; 57: 626-628.
    CrossrefPubMedGoogle Scholar
  • 83 Perkhofer S, Trappl K, Nussbaumer W. et al. Potential synergistic activity of antimycotic substances in combination with human platelets against Aspergillus fumigatus. J Antimicrob Chemother 2010; 8: 1309-1311.
    PubMedGoogle Scholar
  • 84 Perkhofer S, Trappl K, Striessnig B. et al. Platelets enhance activity of antimycotic substances against non-Aspergillus fumigatus Aspergillus species in vitro. Med Mycol 2011; 49: 157-166.
    CrossrefPubMedGoogle Scholar
  • 85 Heller I, Leitner S, Dierich MP. et al. Serotonin (5-HT) enhances the activity of amphotericin B against Aspergillus fumigatus in vitro. Int J Antimicrob Agents 2004; 24: 401-404.
    CrossrefPubMedGoogle Scholar
  • 86 Cossu AP, Musu M, Mura P. et al. Linezolid-induced thrombocytopenia in impaired renal function: is it time for a dose adjustment? A case report and review of literature. Eur J Clin Pharmacol 2014; 70: 23-28.
    CrossrefPubMedGoogle Scholar
  • 87 Hansson EK, Wallin JE, Lindman H. et al. Limited inter-occasion variability in relation to inter-individual variability in chemotherapy-induced myelosuppression. Cancer Chemother Pharmacol 2010; 65: 839-848.
    CrossrefPubMedGoogle Scholar
  • 88 Arnold DM, Nazi I, Warkentin TE. et al. Approach to the diagnosis and management of drug-induced immune thrombocytopenia. Transfus Med Rev 2013; 27: 137-145.
    CrossrefPubMedGoogle Scholar
  • 89 Pavanetto M, Zarpellon A, Giacomini D. et al. Inhibitory effect by new mono-cyclic 4-alkyliden-beta-lactam compounds on human platelet activation. Platelets 2007; 18: 357-364.
    CrossrefPubMedGoogle Scholar
  • 90 Scharf RE. Drugs that affect platelet function. Semin Thromb Hemost 2012; 38: 865-883.
    Article in Thieme ConnectPubMedGoogle Scholar