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2017 ; 15
(1
): 32
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CRAMP deficiency leads to a pro-inflammatory phenotype and impaired phagocytosis
after exposure to bacterial meningitis pathogens
#MMPMID28915816
Kress E
; Merres J
; Albrecht LJ
; Hammerschmidt S
; Pufe T
; Tauber SC
; Brandenburg LO
Cell Commun Signal
2017[Sep]; 15
(1
): 32
PMID28915816
show ga
BACKGROUND: Antimicrobial peptides are important components of the host defence
with a broad range of functions including direct antimicrobial activity and
modulation of inflammation. Lack of cathelin-related antimicrobial peptide
(CRAMP) was associated with higher mortality and bacterial burden and impaired
neutrophil granulocyte infiltration in a model of pneumococcal meningitis. The
present study was designed to characterize the effects of CRAMP deficiency on
glial response and phagocytosis after exposure to bacterial stimuli. METHODS:
CRAMP-knock out and wildtype glial cells were exposed to bacterial supernatants
from Streptococcus pneumoniae and Neisseria meningitides or the bacterial cell
wall components lipopolysaccharide and peptidoglycan. Cell viability, expression
of pro- and anti-inflammatory mediators and activation of signal transduction
pathways, phagocytosis rate and glial cell phenotype were investigated by means
of cell viability assays, immunohistochemistry, real-time RT-PCR and Western
blot. RESULTS: CRAMP-deficiency was associated with stronger expression of
pro-inflammatory and weakened expression of anti-inflammatory cytokines
indicating a higher degree of glial cell activation even under resting-state
conditions. Furthermore, increased translocation of nuclear factor
'kappa-light-chain-enhancer' of activated B-cells was observed and phagocytosis
of S. pneumoniae was reduced in CRAMP-deficient microglia indicating impaired
antimicrobial activity. CONCLUSIONS: In conclusion, the present study detected
severe alterations of the glial immune response due to lack of CRAMP. The results
indicate the importance of CRAMP to maintain and regulate the delicate balance
between beneficial and harmful immune response in the brain.