Induction of the antimicrobial peptide CRAMP in the blood-brain barrier and meninges after meningococcal infection.
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.
Bergman
Peter
P
Department of Medical Biochemistry and Biophysics, Scheeles vag 2, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Johansson
Linda
L
Wan
Hong
H
Jones
Allison
A
Gallo
Richard L
RL
Gudmundsson
Gudmundur H
GH
Hökfelt
Tomas
T
Jonsson
Ann-Beth
AB
Agerberth
Birgitta
B
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000737:chemistry / Q000378:metabolism*; D001923:Brain Chemistry; D054804:Cathelicidins; D007150:Immunohistochemistry; D008578:Meninges / Q000737:chemistry / Q000378:metabolism*; D008589:Meningococcal Infections / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009345:Neisseria meningitidis / Q000187:drug effects / Q000254:growth & development; D018805:Sepsis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology
D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins