title: New insights into the antimicrobial effect of mast cells against Enterococcus faecalis.
abstract: Enterococcus faecalis has emerged as an important cause of life-threatening multidrug-resistant bacterial infections in the hospital setting. The pathogenesis of enterococcal infections has remained a relatively neglected field despite their obvious clinical relevance. The objective of this study was to characterize the interactions between mast cells (MCs), an innate immune cell population abundant in the intestinal lamina propria, and E. faecalis. This study was conducted with primary bone marrow-derived murine MCs. The results demonstrated that MCs exerted an antimicrobial effect against E. faecalis that was mediated both by degranulation, with the concomitant discharge of the antimicrobial effectors contained in the granules, and by the release of extracellular traps, in which E. faecalis was snared and killed. In particular, the cathelicidin LL-37 released by the MCs had potent antimicrobial effect against E. faecalis. We also investigated the specific receptors involved in the recognition of E. faecalis by MCs. We found that Toll-like receptors (TLRs) are critically involved in the MC recognition of E. faecalis, since MCs deficient in the expression of MyD88, an adaptor molecule required for signaling by most TLRs, were significantly impaired in their capacity to degranulate, to reduce E. faecalis growth as well as to release tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) after encountering this pathogen. Furthermore, TLR2 was identified as the most prominent TLR involved in the recognition of E. faecalis by MCs. The results of this study indicate that MCs may be important contributors to the host innate immune defenses against E. faecalis.
authors.affiliation: Infection Immunology Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheb-Wetzel
authors.affiliation: Central Facility for Microscopy, Helmholtz Center for Infection Research, Braunschweig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Bravo
authors.affiliation: Infection Immunology Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany oliver.goldmann@helmholtz-hzi.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Goldmann
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001854:Bone Marrow Cells / Q000502:physiology; D002478:Cells, Cultured; D013293:Enterococcus faecalis / Q000502:physiology* / Q000648:ultrastructure; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000382:microbiology*; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism
chemical_list: C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2
references.citation: Nat Rev Microbiol. 2012 Mar 16;10(4):266-78
references.pmid: 22421879
references.citation: Proteomics. 2009 Dec;9(24):5425-36
references.pmid: 19834908
references.citation: Infect Immun. 2000 May;68(5):2748-55
references.pmid: 10768969
references.citation: J Immunol. 2003 Mar 1;170(5):2274-8
references.pmid: 12594247
references.citation: J Leukoc Biol. 2013 Dec;94(6):1275-84
references.pmid: 23964117
references.citation: Curr Opin Immunol. 2007 Feb;19(1):31-8
references.pmid: 17126541
references.citation: Blood. 2008 Mar 15;111(6):3070-80
references.pmid: 18182576
references.citation: Int J Hematol. 2007 Aug;86(2):158-62
references.pmid: 17875531
references.citation: Exp Biol Med (Maywood). 2001 Dec;226(11):1003-15
references.pmid: 11743136
references.citation: Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):19002-7
references.pmid: 20956325
references.citation: Infect Immun. 1997 Sep;65(9):3501-8
references.pmid: 9284112
references.citation: J Immunol. 2012 Jun 1;188(11):5604-11
references.pmid: 22529298
references.citation: Clin Microbiol Infect. 2010 Jun;16(6):541-54
references.pmid: 20569265
references.citation: Prog Clin Biol Res. 1989;297:155-61; discussion 161
references.pmid: 2685819
references.citation: Crit Rev Oral Biol Med. 2004 Sep 01;15(5):308-20
references.pmid: 15470268
references.citation: Int J Infect Dis. 2007 May;11 Suppl 1:S1-6
references.pmid: 17603948
references.citation: Mol Microbiol. 2002 Oct;46(1):157-68
references.pmid: 12366839
references.citation: Immunobiology. 2009;214(4):321-30
references.pmid: 19327548
references.citation: Infect Immun. 1994 Mar;62(3):987-93
references.pmid: 8112874
references.citation: Int J Med Microbiol. 2013 Aug;303(6-7):360-79
references.pmid: 23602510
references.citation: Trends Immunol. 2002 Mar;23(3):151-8
references.pmid: 11864844
references.citation: Virulence. 2012 Aug 15;3(5):421-33
references.pmid: 23076243
references.citation: Emerg Infect Dis. 2001 Mar-Apr;7(2):183-7
references.pmid: 11294702
references.citation: Curr Protoc Immunol. 2010 Nov;Chapter 7:Unit7.38
references.pmid: 21053305
references.citation: J Biol Chem. 1989 Oct 15;264(29):17462-8
references.pmid: 2677007
references.citation: Expert Opin Pharmacother. 2013 Oct;14(14):1919-32
references.pmid: 23876168
references.citation: J Immunol. 2010 Feb 15;184(4):2116-23
references.pmid: 20083654
references.citation: Cell Microbiol. 2013 Dec;15(12):2034-50
references.pmid: 23869968
references.citation: J Bacteriol. 2013 Jul;195(13):2971-81
references.pmid: 23625841
references.citation: J Antimicrob Chemother. 2013 Mar;68(3):610-8
references.pmid: 23134677
references.citation: J Invest Dermatol. 2014 Nov;134(11):2728-2736
references.pmid: 24844861
references.citation: Nat Rev Immunol. 2007 Feb;7(2):93-104
references.pmid: 17259966
references.citation: J Proteomics. 2014 Jun 25;106:46-60
references.pmid: 24769240
references.citation: Science. 2000 Aug 4;289(5480):785-8
references.pmid: 10926542
references.citation: Methods Mol Biol. 2006;315:363-81
references.pmid: 16110170
references.citation: FASEB J. 1996 May;10(7):731-40
references.pmid: 8635690
references.citation: Antimicrob Agents Chemother. 2001 May;45(5):1558-60
references.pmid: 11302828
references.citation: Microbiology (Reading). 2009 Jun;155(Pt 6):1749-1757
references.pmid: 19383684
references.citation: FEMS Immunol Med Microbiol. 2011 Feb;61(1):94-102
references.pmid: 21073545
references.citation: N Engl J Med. 2002 Oct 10;347(15):1151-60
references.pmid: 12374875
references.citation: Infect Control Hosp Epidemiol. 2008 Nov;29(11):996-1011
references.pmid: 18947320
references.citation: J Cell Biol. 2007 Jan 15;176(2):231-41
references.pmid: 17210947
references.citation: J Immunol. 1994 Apr 15;152(8):4062-9
references.pmid: 8144971
references.citation: Clin Infect Dis. 2000 Sep;31 Suppl 4:S139-43
references.pmid: 11017863
references.citation: J Innate Immun. 2011;3(5):495-507
references.pmid: 21654154
references.citation: Expert Rev Anti Infect Ther. 2008 Oct;6(5):637-55
references.pmid: 18847403
references.citation: PLoS Pathog. 2012;8(4):e1002619
references.pmid: 22577358
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9541-6
references.pmid: 9689116
references.citation: Nat Rev Immunol. 2004 Oct;4(10):787-99
references.pmid: 15459670
references.citation: J Clin Invest. 2011 Apr;121(4):1471-83
references.pmid: 21364279
references.citation: Infect Immun. 1998 Dec;66(12):6030-4
references.pmid: 9826392
references.citation: J Bacteriol. 2006 Feb;188(3):1011-21
references.pmid: 16428405
references.citation: Int J Biochem Cell Biol. 2003 Dec;35(12):1601-7
references.pmid: 12962699