Formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis

Abstract BackgroundBacterial meningitis is, despite progress in research and the development of new treatment strategies, still a cause of severe neurological disability. The brain is protected from penetrating pathogens by the blood-brain barrier and the innate immune system. The invading pathogens are recognized by pattern recognition receptors including the G-protein coupled formyl peptide receptors (FPRs), which are expressed by immune cells of the central nervous system. FPRs show a broad spectrum of ligands including pro- and anti-inflammatory ones. Here, we investigated the effects of the AnnexinA1 mimetic peptide Ac2-26 in a mouse model of pneumococcal meningitis.MethodsWildtype (WT), Fpr1 and Fpr2-deficient mice were intrathecally infected with Streptococcus pneumoniae D39 (type 2). Subsequently, the different mice groups were treated by intraperitoneal injections of Ac2-26 (1 mg/kg body weight) 2, 8 and 24 hour after the infection. The extent of inflammation was analyzed in various brain regions by means of immunohistochemistry and real-time RT-PCR 30 h after infection.ResultsAc2-26 treated mice showed less severe neutrophil infiltration, paralleled by a reduced induction of pro-inflammatory glia cell responses. While meningitis was ameliorated in Ac2-26-treated Fpr1-deficient mice, this protective effect was not observed in Fpr2-deficient mice.ConclusionsEven with appropriate antimicrobial therapy, mortality during bacterial meningitis is high and so attention has recently focused on adjunctive therapies. Our results suggest that Ac2-26 might be a novel adjunctive therapy for Streptococcus pneumoniae-induced meningitis.* The two last authors contributed equally to this study.