title: Role of the cathelicidin-related antimicrobial peptide in inflammation and mortality in a mouse model of bacterial meningitis.
abstract: Antimicrobial peptides (AP) are important components of the innate immune system, yet little is known about their expression and function in the brain. Our previous work revealed upregulated gene expression of cathelicidin-related AP (CRAMP) following bacterial meningitis in primary rat glial cells as well as bactericidal activity against frequent meningitis-causing bacteria. However, the effect of cathelicidin expression on the progression of inflammation and mortality in bacterial meningitis remains unknown. Therefore, we used CRAMP-deficient mice to investigate the effect of CRAMP on bacterial growth, inflammatory responses and mortality in meningitis. Meningitis was induced by intracerebral injection of type 3 Streptococcus pneumoniae. The degree of inflammation was analyzed in various brain regions by means of immunohistochemistry and real-time RT-PCR. CRAMP deficiency led to a higher mortality rate that was associated with increased bacterial titers in the cerebellum, blood and spleen as well as decreased meningeal neutrophil infiltration. CRAMP-deficient mice displayed a higher degree of glial cell activation that was accompanied by a more pronounced proinflammatory response. Taken together, this work provides insight into the important role of CRAMP as part of the innate immune defense against pathogens in bacterial CNS infections.
authors: Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany.
authors: Julika
authors: J
authors: Merres
authors: Jonas
authors: J
authors: Höss
authors: Lea-Jessica
authors: LJ
authors: Albrecht
authors: Eugenia
authors: E
authors: Kress
authors: Oliver
authors: O
authors: Soehnlein
authors: Sandra
authors: S
authors: Jansen
authors: Thomas
authors: T
authors: Pufe
authors: Simone C
authors: SC
authors: Tauber
authors: Lars-Ove
authors: LO
authors: Brandenburg
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053471:Caspases, Initiator; D054804:Cathelicidins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008586:Meningitis, Pneumococcal / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000276:immunology; D015996:Survival Rate; D059467:Transcriptome / Q000276:immunology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; D020170:Caspase 1
references: Int Rev Immunol. 2011 Feb;30(1):16-34
references: 21235323
references: Nat Med. 2006 Jun;12(6):636-41
references: 16751768
references: J Neuroinflammation. 2012 Jul 10;9:168
references: 22781194
references: Mol Neurodegener. 2012 Nov 20;7:55
references: 23164356
references: Cell. 2004 May 28;117(5):561-74
references: 15163405
references: Physiol Rev. 2011 Apr;91(2):461-553
references: 21527731
references: J Immunol. 2012 Jul 1;189(1):304-11
references: 22634613
references: Infect Immun. 2006 Dec;74(12):6982-91
references: 17030578
references: Clin Microbiol Rev. 2011 Jul;24(3):557-91
references: 21734248
references: Neurobiol Dis. 2004 Jun;16(1):133-8
references: 15207270
references: Acta Neuropathol. 2001 May;101(5):499-508
references: 11484822
references: J Neuropathol Exp Neurol. 2008 Nov;67(11):1041-54
references: 18957897
references: J Neuroimmune Pharmacol. 2009 Dec;4(4):448-61
references: 19728102
references: J Neurosci. 2011 Sep 14;31(37):13028-38
references: 21917786
references: Curr Opin Infect Dis. 2002 Jun;15(3):253-7
references: 12015459
references: J Biol Chem. 1997 May 16;272(20):13088-93
references: 9148921
references: Immunology. 2010 Feb;129(2):154-69
references: 20561356
references: Front Biosci. 2008 May 01;13:3760-7
references: 18508470
references: Infect Immun. 2013 May;81(5):1788-97
references: 23478321
references: Br J Dermatol. 2007 Dec;157(6):1124-31
references: 17916212
references: J Infect Dis. 1997 Sep;176(3):693-7
references: 9291317
references: Int J Biochem Cell Biol. 1999 Jun;31(6):645-51
references: 10404637
references: Brain. 2001 Sep;124(Pt 9):1734-42
references: 11522576
references: Antimicrob Agents Chemother. 2004 May;48(5):1526-33
references: 15105101
references: Curr Opin Infect Dis. 2010 Jun;23(3):217-23
references: 20216309
references: Curr Issues Mol Biol. 2005 Jul;7(2):179-96
references: 16053249
references: BMC Infect Dis. 2010 Jan 03;10:1
references: 20044936
references: Cell. 2008 Mar 7;132(5):818-31
references: 18329368
references: Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4498-508
references: 17898271
references: Cell Mol Life Sci. 2003 Mar;60(3):536-49
references: 12737313
references: Blood. 2008 Aug 15;112(4):1461-71
references: 18490516
references: N Engl J Med. 2004 Oct 28;351(18):1849-59
references: 15509818
references: J Neurochem. 2006 Oct;99(1):1-12
references: 16899072
references: Eur Cytokine Netw. 1997 Dec;8(4):375-81
references: 9459617
references: Circ Res. 2013 Mar 1;112(5):792-801
references: 23283724
references: J Neuroimmunol. 2009 Dec 10;217(1-2):55-64
references: 19879657
references: Apoptosis. 2009 Apr;14(4):522-35
references: 19156527
references: Arch Immunol Ther Exp (Warsz). 2010 Oct;58(5):365-77
references: 20668978
references: FASEB J. 2001 Aug;15(10):1819-21
references: 11481241
references: Acta Med Scand. 1978;203(1-2):71-4
references: 626116
references: Brain Res. 2010 Apr 22;1326:1-14
references: 20176000
references: Int J Crit Illn Inj Sci. 2012 May;2(2):82-97
references: 22837896
references: J Infect Dis. 2002 Oct 1;186(7):1047-52
references: 12232850
references: J Immunol. 2012 Feb 15;188(4):1992-2000
references: 22246630
references: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3507-12
references: 23401516
references: J Neuroimmunol. 2013 Feb 15;255(1-2):18-31
references: 23141747
references: Nature. 2001 Nov 22;414(6862):454-7
references: 11719807
references: J Clin Invest. 2012 Apr;122(4):1164-71
references: 22466658
references: FASEB J. 1993 Apr 1;7(6):592-600
references: 8472896
references: Cochrane Database Syst Rev. 2010 Sep 08;(9):CD004405
references: 20824838
references: Med Princ Pract. 2008;17(1):76-9
references: 18059106
references: J Neuropathol Exp Neurol. 2005 Sep;64(9):806-15
references: 16141791
references: Curr Opin Neurol. 2010 Jun;23(3):312-8
references: 20442574