Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis

Brandenburg, Lars-Ove; Varoga, Deike; Nicolaeva, Nicoletta; Leib, Stephen L.; Wilms, Henrik; Podschun, Rainer; Wruck, Christoph J; Schröder, Jens-Michael; Pufe, Thomas; Lucius, Ralph (2008). Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis. Journal of neuropathology and experimental neurology, 67(11), pp. 1041-1054. Hagerstown, Md.: Lippincott Williams & Wilkins 10.1097/NEN.0b013e31818b4801

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Leib, Stephen

ISSN:

0022-3069

ISBN:

18957897

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:06

Last Modified:

23 Jul 2015 09:09

Publisher DOI:

10.1097/NEN.0b013e31818b4801

PubMed ID:

18957897

Web of Science ID:

000260590300004

BORIS DOI:

10.7892/boris.28668

URI:

https://boris.unibe.ch/id/eprint/28668 (FactScience: 125107)

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