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

Authors
  • Rüger, Marvin1, 2
  • Kipp, Eugenia1, 2
  • Schubert, Nadine1, 2
  • Schröder, Nicole1, 2
  • Pufe, Thomas2
  • Stope, Matthias B.3, 4
  • Kipp, Markus1, 5
  • Blume, Christian6
  • Tauber, Simone C.7
  • Brandenburg, Lars-Ove1, 2, 5
  • 1 Rostock University Medical Center, Gertrudenstrasse 9, Rostock, 18057, Germany , Rostock (Germany)
  • 2 RWTH Aachen University, Aachen, Germany , Aachen (Germany)
  • 3 University Medicine Greifswald, Greifswald, Germany , Greifswald (Germany)
  • 4 University Hospital Bonn, Bonn, Germany , Bonn (Germany)
  • 5 Rostock University Medical Center, Gelsheimer Strasse 20, Rostock, 18147, Germany , Rostock (Germany)
  • 6 RWTH Aachen University, Pauwelsstrasse 30, Aachen, 52074, Germany , Aachen (Germany)
  • 7 RWTH University Hospital Aachen, Aachen, Germany , Aachen (Germany)
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Oct 29, 2020
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12974-020-02006-w
Source
Springer Nature
Keywords
License
Green

Abstract

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.

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