Role of the Cathelicidin-Related Antimicrobial Peptide in Inflammation and Mortality in a Mouse Model of Bacterial Meningitis

Abstract

Antimicrobial peptides (AP) are important components of the innate immune system, yet little is known about their expression and function in the brain. Our previous work revealed upregulated gene expression of cathelicidin-related AP (CRAMP) following bacterial meningitis in primary rat glial cells as well as bactericidal activity against frequent meningitis-causing bacteria. However, the effect of cathelicidin expression on the progression of inflammation and mortality in bacterial meningitis remains unknown. Therefore, we used CRAMP-deficient mice to investigate the effect of CRAMP on bacterial growth, inflammatory responses and mortality in meningitis. Meningitis was induced by intracerebral injection of type 3 Streptococcus pneumoniae. The degree of inflammation was analyzed in various brain regions by means of immunohistochemistry and real-time RT-PCR. CRAMP deficiency led to a higher mortality rate that was associated with increased bacterial titers in the cerebellum, blood and spleen as well as decreased meningeal neutrophil infiltration. CRAMP-deficient mice displayed a higher degree of glial cell activation that was accompanied by a more pronounced proinflammatory response. Taken together, this work provides insight into the important role of CRAMP as part of the innate immune defense against pathogens in bacterial CNS infections. © 2013 S. Karger AG, Basel

Lack of formyl peptide receptor 1 and 2 leads to more severe inflammation and higher mortality in mice with of pneumococcal meningitis

“…The mice suffered from increased inflammation and mortality response after infection. 26 In conclusion, our results reveal the importance of the formyl peptide receptors for the host defense in a mouse model of pneumococcal meningitis. Our results provide interesting insights into the function of the innate immune system during the course of bacterial meningitis.…”

LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent infection by uropathogenic bacteria

“…6b). As cathelicidin 21 , Reg3g 22 and a-defensin-5 (ref. 23) have been supposed to have bactericidal function, we next further investigated their expression of in WT and Lrrc19 KO mice infected with UPEC.…”

2-O-Sulfated Domains in Syndecan-1 Heparan Sulfate Inhibit Neutrophil Cathelicidin and Promote Staphylococcus aureus Corneal Infection

“…Although the normal functions of syndecan-1 in the cornea remain to be elucidated, our findings suggest a possible beneficial role of inhibiting syndecan-1 HS and, in particular, the activity of 2-O-sulfated HS domains in treating S. aureus keratitis, for which new interventions are needed. Furthermore, CRAMP is not only important for host defense against S. aureus, but has also been shown to be critical in infections caused by other major pathogens of the ocular surface, such as P. aeruginosa (54) and S. pneumoniae (68). These observations suggest that neutralizing syndecan-1 HS to enhance CRAMP activity may be a viable option for the treatment of infectious keratitis caused by multiple bacterial pathogens of the ocular surface.…”