See the published version of this article at Journal of Neuroinflammation.
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Formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis
Lars-Ove Brandenburg
Universitatsmedizin Rostock
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6126-8153
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Neuroinflammation.
Background
Bacterial 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.
Methods
Wildtype (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.
Results
Ac2-26 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.
Conclusions
Even 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.
Keywords
bacterial meningitis, formyl peptide receptor, glia cell, innate immunity, Streptococcus pneumoniae, Annexin A1
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CURRENT STATUS: Published
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On 29 Oct, 2020
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Editorial decision: Major Revision
On 09 Jun, 2020
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Received 06 Jun, 2020
Review #2 received
Received 03 Jun, 2020
Review #1 received
Received 03 Jun, 2020
Reviewer #3 agreed
On 30 May, 2020
Reviewer #1 agreed
On 24 May, 2020
Reviewer #2 agreed
On 24 May, 2020
Reviewers invited
Invitations sent on 22 May, 2020
Editor assigned
On 15 May, 2020
First submitted
On 14 May, 2020
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On 14 May, 2020
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On 14 May, 2020
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Subject Areas
Neurobiology of Disease
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This preprint is under consideration at Journal of Neuroinflammation. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis
Lars-Ove Brandenburg
Universitatsmedizin Rostock
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6126-8153
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 1
Posted 19 May, 2020
Published
On 29 Oct, 2020
No community comments so far
Editorial decision: Major Revision
On 09 Jun, 2020
Review #3 received
Received 06 Jun, 2020
Review #2 received
Received 03 Jun, 2020
Review #1 received
Received 03 Jun, 2020
Reviewer #3 agreed
On 30 May, 2020
Reviewer #1 agreed
On 24 May, 2020
Reviewer #2 agreed
On 24 May, 2020
Reviewers invited
Invitations sent on 22 May, 2020
Editor assigned
On 15 May, 2020
First submitted
On 14 May, 2020
Submission checks complete
On 14 May, 2020
Editor invited
On 14 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Neuroinflammation.
Background
Bacterial 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.
Methods
Wildtype (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.
Results
Ac2-26 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.
Conclusions
Even 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5