CRAMP deficiency leads to a pro-inflammatory phenotype and impaired phagocytosis after exposure to bacterial meningitis pathogens

Cell Communication and Signaling

Research

Sven Hammerschmidt¹  Thomas Pufe²  Eugenia Kress²  Lars-Ove Brandenburg²  Julika Merres²  Lea-Jessica Albrecht²  Simone C. Tauber³ 

[1] Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany;Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 52074, Aachen, Germany;Department of Neurology, RWTH University Hospital Aachen, Aachen, Germany;

关键词: Antimicrobial peptide;    Cathelicidin;    Cramp;    Glial cell;    Innate immunity;    Signal transduction;   

DOI  :  10.1186/s12964-017-0190-1

 received in 2017-05-08, accepted in 2017-09-12,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAntimicrobial 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.MethodsCRAMP-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.ResultsCRAMP-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.ConclusionsIn 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.

【 授权许可】

CC BY   
© The Author(s). 2017