The Formyl Peptid Receptor Ligand Ac2-26 Improves the Integrity of the Blood−Brain Barrier in the Course of Pneumococcal Meningitis
Year: 2024
Type: article
Abstract: Background: The brain is protected from invading pathogens by the blood−brain barrier (BBB) and the innate immune system. Pattern recognition receptors play a crucial role in detecting bacteria and initiating the innate immune response. Among these are G-protein-coupled formyl peptide receptors (FPR), which are expressed by immune cells in the central nervous system. In this study, we investigated the influence of the FPR ligand Ac2-26 on the integrity of the BBB during pneumococcal meningitis. Methods: Wild-type (WT) and Fpr1- and Fpr2-deficient mice were intrathecally infected with Streptococcus pneumoniae. Subsequently, different groups of mice were treated with intraperitoneal injections of Ac2-26. The integrity of the BBB was analyzed using various markers through immunohistochemistry and immunofluorescence. Results: The results showed reduced BBB integrity during the course of bacterial meningitis. Treatment with Ac2-26 in WT mice significantly prolonged the maintenance of BBB integrity. However, this effect was not observed in Fpr2-deficient mice. Conclusions: This study extends previous findings on the anti-inflammatory properties of Ac2-26 by demonstrating that Ac2-26 positively affects BBB integrity via FPR2 during pneumococcal meningitis. These findings suggest that further investigation of Ac2-26 and other FPR modulators as potential therapies for Streptococcus pneumoniae-induced meningitis is warranted.
Source: Cells
Authors: Johannes Deutloff, Irina Pöhner, Johann Rößler, Markus Kipp, Simone C. Tauber, Lars-Ove Brandenburg
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,069
Funder: Deutsche Forschungsgemeinschaft
Award: G3257747622
OpenAlex ID: W4405604428