The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis
Abstract Background Bacterial 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-coupl...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-10-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-020-02006-w |
| _version_ | 1819136079257665536 |
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| author | Marvin Rüger Eugenia Kipp Nadine Schubert Nicole Schröder Thomas Pufe Matthias B. Stope Markus Kipp Christian Blume Simone C. Tauber Lars-Ove Brandenburg |
| author_facet | Marvin Rüger Eugenia Kipp Nadine Schubert Nicole Schröder Thomas Pufe Matthias B. Stope Markus Kipp Christian Blume Simone C. Tauber Lars-Ove Brandenburg |
| author_sort | Marvin Rüger |
| collection | DOAJ |
| description | Abstract Background Bacterial 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. Methods Wildtype (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. Results Ac2-26-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. Conclusions In 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. |
| first_indexed | 2024-12-22T10:29:16Z |
| format | Article |
| id | doaj.art-2b8d3fb8b72d4a9390405b18948b8297 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-22T10:29:16Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-2b8d3fb8b72d4a9390405b18948b82972022-12-21T18:29:22ZengBMCJournal of Neuroinflammation1742-20942020-10-0117111410.1186/s12974-020-02006-wThe formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitisMarvin Rüger0Eugenia Kipp1Nadine Schubert2Nicole Schröder3Thomas Pufe4Matthias B. Stope5Markus Kipp6Christian Blume7Simone C. Tauber8Lars-Ove Brandenburg9Institute of Anatomy, Rostock University Medical CenterInstitute of Anatomy, Rostock University Medical CenterInstitute of Anatomy, Rostock University Medical CenterInstitute of Anatomy, Rostock University Medical CenterDepartment of Anatomy and Cell Biology, RWTH Aachen UniversityDepartment of Urology, University Medicine GreifswaldInstitute of Anatomy, Rostock University Medical CenterDepartment of Neurosurgery, RWTH Aachen UniversityDepartment of Neurology, RWTH University Hospital AachenInstitute of Anatomy, Rostock University Medical CenterAbstract Background Bacterial 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. Methods Wildtype (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. Results Ac2-26-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. Conclusions In 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.http://link.springer.com/article/10.1186/s12974-020-02006-wBacterial meningitisFormyl peptide receptorGlial cellInnate immunityStreptococcus pneumoniaeAnnexin A1 |
| spellingShingle | Marvin Rüger Eugenia Kipp Nadine Schubert Nicole Schröder Thomas Pufe Matthias B. Stope Markus Kipp Christian Blume Simone C. Tauber Lars-Ove Brandenburg The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis Journal of Neuroinflammation Bacterial meningitis Formyl peptide receptor Glial cell Innate immunity Streptococcus pneumoniae Annexin A1 |
| title | The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis |
| title_full | The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis |
| title_fullStr | The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis |
| title_full_unstemmed | The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis |
| title_short | The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis |
| title_sort | formyl peptide receptor agonist ac2 26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis |
| topic | Bacterial meningitis Formyl peptide receptor Glial cell Innate immunity Streptococcus pneumoniae Annexin A1 |
| url | http://link.springer.com/article/10.1186/s12974-020-02006-w |
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