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

Journal of Neuroinflammation

Thomas Pufe¹  Simone C. Tauber²  Christian Blume³  Matthias B. Stope⁴  Markus Kipp⁵  Nadine Schubert⁶  Marvin Rüger⁶  Nicole Schröder⁶  Eugenia Kipp⁶  Lars-Ove Brandenburg⁷ 

[1] Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany;Department of Neurology, RWTH University Hospital Aachen, Aachen, Germany;Department of Neurosurgery, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany;Department of Urology, University Medicine Greifswald, Greifswald, Germany;Department of Gynecology and Obstetrics, University Hospital Bonn, Bonn, Germany;Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057, Rostock, Germany;Center for Transdisciplinary Neurosciences Rostock (CTNR), Rostock University Medical Center, Gelsheimer Strasse 20, 18147, Rostock, Germany;Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057, Rostock, Germany;Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany;Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057, Rostock, Germany;Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany;Center for Transdisciplinary Neurosciences Rostock (CTNR), Rostock University Medical Center, Gelsheimer Strasse 20, 18147, Rostock, Germany;

关键词: Bacterial meningitis;    Formyl peptide receptor;    Glial cell;    Innate immunity;    Streptococcus pneumoniae;    Annexin A1;   

DOI  :  10.1186/s12974-020-02006-w

来源: Springer

【 摘 要 】

BackgroundBacterial meningitis is 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 annexin A1 mimetic peptide Ac2-26 in a mouse model of pneumococcal meningitis.MethodsWildtype (WT) and 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 h post-infection. The extent of inflammation was analyzed in various brain regions by means of immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR) 30 h post-infection.ResultsAc2-26-treated WT mice showed less severe neutrophil infiltration, paralleled by a reduced induction of pro-inflammatory glial cell responses in the hippocampal formation and cortex. While meningitis was ameliorated in Ac2-26-treated Fpr1-deficient mice, this protective effect was not observed in Fpr2-deficient mice. Irrespective of Ac2-26 treatment, inflammation was more severe in Fpr2-deficient compared to Fpr1-deficient mice.ConclusionsIn summary, this study demonstrates anti-inflammatory properties of Ac2-26 in a model of bacterial meningitis, which are mediated via FPR2, but not FPR1. Ac2-26 and other FPR2 modulators might be promising targets for the development of novel therapies for Streptococcus pneumoniae-induced meningitis.

【 授权许可】

CC BY