Novel Anti-bacterial Activities of β-defensin 1 in Human Platelets: Suppression of Pathogen Growth and Signaling of Neutrophil Extracellular Trap Formation

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Human β-defensins (hBD) are antimicrobial peptides that curb microbial activity. Although hBD's are primarily expressed by epithelial cells, we show that human platelets express hBD-1 that has both predicted and novel antibacterial activities. We observed that activated platelets surround Staphylococcus aureus (S. aureus), forcing the pathogens into clusters that have a reduced growth rate compared to S. aureus alone. Given the microbicidal activity of β-defensins, we determined whether hBD family members were present in platelets and found mRNA and protein for hBD-1. We also established that hBD-1 protein resided in extragranular cytoplasmic compartments of platelets. Consistent with this localization pattern, agonists that elicit granular secretion by platelets did not readily induce hBD-1 release. Nevertheless, platelets released hBD-1 when they were stimulated by α-toxin, a S. aureus product that permeabilizes target cells. Platelet-derived hBD-1 significantly impaired the growth of clinical strains of S. aureus. hBD-1 also induced robust neutrophil extracellular trap (NET) formation by target polymorphonuclear leukocytes (PMNs), which is a novel antimicrobial function of β-defensins that was not previously identified. Taken together, these data demonstrate that hBD-1 is a previously-unrecognized component of platelets that displays classic antimicrobial activity and, in addition, signals PMNs to extrude DNA lattices that capture and kill bacteria.

Vyšlo v časopise: Novel Anti-bacterial Activities of β-defensin 1 in Human Platelets: Suppression of Pathogen Growth and Signaling of Neutrophil Extracellular Trap Formation. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002355
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002355

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1. DurackDT 1975 Experimental bacterial endocarditis. IV. Structure and evolution of very early lesions. J Pathol 115 81 89

2. FitzgeraldJRFosterTJCoxD 2006 The interaction of bacterial pathogens with platelets. Nat Rev Microbiol 4 445 457

3. YeamanMBayerAS 2007 Antimicrobial Host Defense. MichelsonAD Platelets San Diego Elsevier Science 469 490

4. YeamanMRPuentesSMNormanDCBayerAS 1992 Partial characterization and staphylocidal activity of thrombin-induced platelet microbicidal protein. Infect Immun 60 1202 1209

5. YeamanMRTangYQShenAJBayerASSelstedME 1997 Purification and in vitro activities of rabbit platelet microbicidal proteins. Infect Immun 65 1023 1031

6. TangYQYeamanMRSelstedME 2002 Antimicrobial peptides from human platelets. Infect Immun 70 6524 6533

7. TecleTTripathiSHartshornKL 2010 Review: Defensins and cathelicidins in lung immunity. Innate Immun 16 151 159

8. GoldmanMJAndersonGMStolzenbergEDKariUPZasloffM 1997 Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 88 553 560

9. BalsRWangXWuZFreemanTBafnaV 1998 Human beta-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung. J Clin Invest 102 874 880

10. GanzTSelstedMESzklarekDHarwigSSDaherK 1985 Defensins. Natural peptide antibiotics of human neutrophils. J Clin Invest 76 1427 1435

11. SelstedMEMillerSIHenschenAHOuelletteAJ 1992 Enteric defensins: antibiotic peptide components of intestinal host defense. J Cell Biol 118 929 936

12. RamasundaraMLeachSTLembergDADayAS 2009 Defensins and inflammation: the role of defensins in inflammatory bowel disease. J Gastroenterol Hepatol 24 202 208

13. PazgierMHooverDMYangDLuWLubkowskiJ 2006 Human beta-defensins. Cell Mol Life Sci 63 1294 1313

14. SelstedMEOuelletteAJ 2005 Mammalian defensins in the antimicrobial immune response. Nat Immunol 6 551 557

15. BrinkmannVReichardUGoosmannCFaulerBUhlemannY 2004 Neutrophil extracellular traps kill bacteria. Science 303 1532 1535

16. YostCCCodyMJHarrisESThorntonNLMcInturffAM 2009 Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates. Blood 113 6419 6427

17. ClarkSRMaACTavenerSAMcDonaldBGoodarziZ 2007 Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 13 463 469

18. DenisMMTolleyNDBuntingMSchwertzHJiangH 2005 Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Cell 122 379 391

19. SchwertzHTolleyNDFoulksJMDenisMMRisenmayBW 2006 Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets. J Exp Med 203 2433 2440

20. SchwertzHKosterSKahrWHMichettiNKraemerBF 2010 Anucleate platelets generate progeny. Blood 115 3801 3809

21. LindemannSTolleyNDEyreJRKraissLWMahoneyTM 2001 Integrins regulate the intracellular distribution of eukaryotic initiation factor 4E in platelets. A checkpoint for translational control. J Biol Chem 276 33947 33951

22. KerriganSWClarkeNLoughmanAMeadeGFosterTJ 2008 Molecular basis for Staphylococcus aureus-mediated platelet aggregate formation under arterial shear in vitro. Arterioscler Thromb Vasc Biol 28 335 340

23. FitzgeraldJRLoughmanAKeaneFBrennanMKnobelM 2006 Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the FcgammaRIIa receptor. Mol Microbiol 59 212 230

24. O'BrienLKerriganSWKawGHoganMPenadesJ 2002 Multiple mechanisms for the activation of human platelet aggregation by Staphylococcus aureus: roles for the clumping factors ClfA and ClfB, the serine-aspartate repeat protein SdrE and protein A. Mol Microbiol 44 1033 1044

25. BieleckiTMGazdzikTSArendtJSzczepanskiTKrolW 2007 Antibacterial effect of autologous platelet gel enriched with growth factors and other active substances: an in vitro study. J Bone Joint Surg Br 89 417 420

26. KooSPYeamanMRBayerAS 1996 Staphylocidal action of thrombin-induced platelet microbicidal protein is influenced by microenvironment and target cell growth phase. Infect Immun 64 3758 3764

27. ReedGL 2007 Platelet Secretion. MichelsonAD Platelets San Diego Elsevier Science 181 195

28. KimJAJungYJSeohJYWooSYSeoJS 2002 Gene expression profile of megakaryocytes from human cord blood CD34(+) cells ex vivo expanded by thrombopoietin. Stem Cells 20 402 416

29. BenschKWRaidaMMagertHJSchulz-KnappePForssmannWG 1995 hBD-1: a novel beta-defensin from human plasma. FEBS Lett 368 331 335

30. FangXMShuQChenQXBookMSahlHG 2003 Differential expression of alpha- and beta-defensins in human peripheral blood. Eur J Clin Invest 33 82 87

31. TohidnezhadMVarogaDPodschunRWruckCJSeekampA 2011 Thrombocytes are effectors of the innate immune system releasing human beta defensin-3. Injury 42 682 686

32. SuppDMKarpinskiACBoyceST 2004 Expression of human beta-defensins HBD-1, HBD-2, and HBD-3 in cultured keratinocytes and skin substitutes. Burns 30 643 648

33. DossMWhiteMRTecleTHartshornKL 2010 Human defensins and LL-37 in mucosal immunity. J Leukoc Biol 87 79 92

34. PawarPShinPKMousaSARossJMKonstantopoulosK 2004 Fluid shear regulates the kinetics and receptor specificity of Staphylococcus aureus binding to activated platelets. J Immunol 173 1258 1265

35. YoussefianTDrouinAMasseJMGuichardJCramerEM 2002 Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Blood 99 4021 4029

36. WhiteJG 2006 Why human platelets fail to kill bacteria. Platelets 17 191 200

37. AlexanderEHHudsonMC 2001 Factors influencing the internalization of Staphylococcus aureus and impacts on the course of infections in humans. Appl Microbiol Biotechnol 56 361 366

38. YeamanMRNormanDCBayerAS 1992 Platelet microbicidal protein enhances antibiotic-induced killing of and postantibiotic effect in Staphylococcus aureus. Antimicrob Agents Chemother 36 1665 1670

39. PetersMJDixonGKotowiczKTHatchDJHeydermanRS 1999 Circulating platelet-neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing. Br J Haematol 106 391 399

40. BayerASRamosMDMenziesBEYeamanMRShenAJ 1997 Hyperproduction of alpha-toxin by Staphylococcus aureus results in paradoxically reduced virulence in experimental endocarditis: a host defense role for platelet microbicidal proteins. Infect Immun 65 4652 4660

41. YeamanMRBayerASKooSPFossWSullamPM 1998 Platelet microbicidal proteins and neutrophil defensin disrupt the Staphylococcus aureus cytoplasmic membrane by distinct mechanisms of action. J Clin Invest 101 178 187

42. AshmarinIPTkachenkoSBRud'koIAKornevaEAKokriakovVN 1993 Effect of defensin on platelet functional activity. Biull Eksp Biol Med 115 23 25

43. YangDChertovOBykovskaiaSNChenQBuffoMJ 1999 Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286 525 528

44. BoniottoMJordanWJEskdaleJTossiAAntchevaN 2006 Human beta-defensin 2 induces a vigorous cytokine response in peripheral blood mononuclear cells. Antimicrob Agents Chemother 50 1433 1441

45. WeyrichASDenisMMKuhlmann-EyreJRSpencerEDDixonDA 2005 Dipyridamole selectively inhibits inflammatory gene expression in platelet-monocyte aggregates. Circulation 111 633 642

46. WeyrichASElstadMRMcEverRPMcIntyreTMMooreKL 1996 Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 97 1525 1534

47. MaACKubesP 2008 Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis. J Thromb Haemost 6 415 420

48. PilsczekFHSalinaDPoonKKFaheyCYippBG 2010 A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol 185 7413 7425

49. SchmidtRBultmannAFischelSGillitzerACullenP 2008 Extracellular matrix metalloproteinase inducer (CD147) is a novel receptor on platelets, activates platelets, and augments nuclear factor kappaB-dependent inflammation in monocytes. Circ Res 102 302 309