Related Experiment Video
Updated: Mar 6, 2026
Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
Published on: February 23, 2014
Role of purinergic signaling in experimental pneumococcal meningitis
Marco Zierhut1, Susanne Dyckhoff1, Ilias Masouris1
1Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Abstract:
Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1β pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR. ATP levels were determined in murine CSF and cell culture experiments. Treatment with the P2R antagonists suramin or brilliant blue G did not have any impact on disease course. This lack of effect might be attributed to meningitis-associated down-regulation of brain P2R expression and/or a drop of cerebrospinal fluid (CSF) ATP, as demonstrated by RT-PCR and ATP analyses. Supplemental cell culture experiments suggest that the reduction in CSF ATP is, at least partly, due to ATP hydrolysis by ectonucleotidases of neutrophils and macrophages. In conclusion, this study suggests that ATP-P2R signaling is only of minor or even no significance in PM. This may be explained by down-regulation of P2R expression and decreased CSF ATP levels.
Insights
This study investigated ATP-P2R signaling in pneumococcal meningitis (PM). Researchers found that blocking P2 purinoceptors (P2Rs) did not affect disease course, suggesting this pathway has minimal impact on PM pathology.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Neutrophilic inflammation exacerbates brain damage in pneumococcal meningitis (PM).
- The NLRP3 inflammasome/interleukin (IL)-1β pathway is a key inflammatory driver in PM.
- The P2X7 receptor (P2R), activated by ATP, is crucial for NLRP3 inflammasome activation.
Purpose of the Study:
- To investigate the role of ATP and P2Rs in the pathogenesis of pneumococcal meningitis.
- To determine if targeting ATP-P2R signaling could be a therapeutic strategy for PM.
Main Methods:
- A mouse model of pneumococcal meningitis was used.
- P2R antagonists (suramin, brilliant blue G) were administered.
- Brain P2R expression was analyzed using RT-PCR.
- Cerebrospinal fluid (CSF) ATP levels were measured.
- In vitro cell culture experiments were performed.
Main Results:
- P2R antagonist treatment did not alter the course of meningitis.
- RT-PCR and ATP analyses revealed down-regulation of brain P2R expression and decreased CSF ATP levels during meningitis.
- Cell culture experiments indicated that neutrophils and macrophages hydrolyze ATP, reducing CSF ATP levels.
Conclusions:
- ATP-P2R signaling appears to have minor or no significance in pneumococcal meningitis.
- Reduced P2R expression and lower CSF ATP levels likely explain the lack of therapeutic effect.
- This suggests that targeting the ATP-P2R pathway may not be an effective treatment for PM.
Related Concept Videos
01:29Pneumonia II: Pathophysiology
01:28Gene Regulation in Microbial Communities: Quorum Sensing