Induction of the Antimicrobial Peptide CRAMP in the Blood-Brain Barrier and Meninges after Meningococcal Infection
- 1 December 2006
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 74 (12) , 6982-6991
- https://doi.org/10.1128/iai.01043-06
Abstract
Antimicrobial peptides are present in most living species and constitute important effector molecules of innate immunity. Recently, we and others have detected antimicrobial peptides in the brain. This is an organ that is rarely infected, which has mainly been ascribed to the protective functions of the blood-brain barrier (BBB) and meninges. Since the bactericidal properties of the BBB and meninges are not known, we hypothesized that antimicrobial peptides could play a role in these barriers. We addressed this hypothesis by infecting mice with the neuropathogenic bacterium Neisseria meningitidis. Brains were analyzed for expression of the antimicrobial peptide CRAMP by immunohistochemistry in combination with confocal microscopy. After infection, we observed induction of CRAMP in endothelial cells of the BBB and in cells of the meninges. To explore the functional role of CRAMP in meningococcal disease, we infected mice deficient of the CRAMP gene. Even though CRAMP did not appear to protect the brain from invasion of meningococci, CRAMP knockout mice were more susceptible to meningococcal infection than wild-type mice and exhibited increased meningococcal growth in blood, liver, and spleen. Moreover, we could demonstrate that carbonate, a compound that accumulates in the circulation during metabolic acidosis, makes meningococci more susceptible to CRAMP.Keywords
This publication has 51 references indexed in Scilit:
- Interaction and Cellular Localization of the Human Host Defense Peptide LL-37 with Lung Epithelial CellsInfection and Immunity, 2005
- Defensins: antimicrobial peptides of innate immunityNature Reviews Immunology, 2003
- Cathelicidins, multifunctional peptides of the innate immunityJournal of Leukocyte Biology, 2003
- Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensinNature, 2003
- Contribution of Human α-Defensin 1, 2, and 3 to the Anti-HIV-1 Activity of CD8 Antiviral FactorScience, 2002
- Toll-Like Receptor 4-Dependent Activation of Dendritic Cells by β-Defensin 2Science, 2002
- Antimicrobial peptides of multicellular organismsNature, 2002
- Innate antimicrobial peptide protects the skin from invasive bacterial infectionNature, 2001
- Cutaneous Injury Induces the Release of Cathelicidin Anti-Microbial Peptides Active Against Group A StreptococcusJournal of Investigative Dermatology, 2001
- Nucleotide Sequence and Expression of Rat β-Defensin-1: Its Significance in Diabetic Rodent ModelsNephron, 2001