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.

Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validation

“…To date, no studies have reported the involvement of these genes in the occurrence and development of CRSwNP. A recent study has confirmed that the formyl peptide receptor agonist Ac2-26 exerts an anti-inflammatory effect in a mouse model of bacterial meningitis through the formamide peptide receptor 2 (FPR2) (Rüger et al, 2020). FPR2 agonists could stimulate the resolution of inflammation by inhibiting neutrophil chemotaxis and stimulating macrophage phagocytosis, which may be the key to the treatment of chronic inflammatory diseases (Asahina et al, 2020).…”