Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis.
Antimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF. We next characterized the expression, secretion, and bactericidal properties of rat cathelin-related antimicrobial peptide, the homologue of the human LL-37, in rat astrocytes and microglia after incubation with different bacterial components. Using real-time polymerase chain reaction and Western blotting, we determined that supernatants from both astrocytes and microglia incubated with bacterial component supernatants had antimicrobial activity. The expression of rat cathelin-related antimicrobial peptide in rat glial cells involved different signal transduction pathways and was induced by the inflammatory cytokines interleukin 1beta and tumor necrosis factor. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae, and rat cathelin-related antimicrobial peptide was localized in glia, choroid plexus, and ependymal cells by immunohistochemistry. Together, these results suggest that cathelicidins produced by glia and other cells play an important part in the innate immune response against pathogens in central nervous system bacterial infections.
Brandenburg
Lars-Ove
LO
Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany. lbradenburg@ukaachen.de
Varoga
Deike
D
Nicolaeva
Nicoletta
N
Leib
Stephen L
SL
Wilms
Henrik
H
Podschun
Rainer
R
Wruck
Christoph J
CJ
Schröder
Jens-Michael
JM
Pufe
Thomas
T
Lucius
Ralph
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000627:therapeutic use; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008586:Meningitis, Pneumococcal / Q000097:blood / Q000134:cerebrospinal fluid*; D008875:Middle Aged; D009113:Muramidase / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D055815:Young Adult; D054804:Cathelicidins
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D009573:Nitrites; D012333:RNA, Messenger; D009113:Muramidase; D054804:Cathelicidins