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Diurnal dynamic behavior of microglia in response to infected bacteria through the UDP-P2Y6 receptor system
Fumiko Takayama1,2, Yoshinori Hayashi1, Zhou Wu1,3
1Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
Abstract:
It has long been believed that microglia morphologically transform into the activated state by retracting their long processes and consuming pathogens when bacteria infect into the brain parenchyma. In the present study, however, we showed for the first time that murine cortical microglia extend their processes towards focally injected Porphyromonas gingivalis. This P. gingivalis-induced microglial process extension was significantly increased during the light (sleeping) phase than the dark (waking) phase. In contrast, focally injected ATP-induced microglial process extension was significantly increased during the dark phase than the light phase. Furthermore, in contrast to the P2Y12 receptor-mediated mechanism of ATP-induced microglial process extension, the P. gingivalis-mediated microglial process extension was mediated by P2Y6 receptors. The infection of bacteria such as P. gingivalis to the brain parenchyma may induce the secretion of UDP from microglia at the site of infection, which in turn induces the process extension of the neighboring microglia.
Insights
Contrary to popular belief, microglia extend processes toward Porphyromonas gingivalis bacteria in the brain. This bacterial response differs from ATP-induced responses and involves P2Y6 receptors.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Microglia are key immune cells in the brain parenchyma.
- Traditionally, microglia were thought to retract processes upon bacterial infection.
- The precise mechanisms of microglial response to bacterial pathogens remain incompletely understood.
Purpose of the Study:
- To investigate the morphological response of murine cortical microglia to bacterial infection.
- To elucidate the signaling pathways and temporal characteristics of microglial process extension in response to Porphyromonas gingivalis.
- To compare microglial responses to bacterial infection versus ATP stimulation.
Main Methods:
- Focal injection of Porphyromonas gingivalis and ATP into the murine cortex.
- Time-lapse imaging to observe microglial process extension.
- Pharmacological inhibition and genetic manipulation to identify receptor involvement (P2Y12, P2Y6).
- Assessment of diurnal variations in microglial responses.
Main Results:
- Murine cortical microglia extended processes towards focally injected Porphyromonas gingivalis, challenging prior assumptions.
- P. gingivalis-induced process extension was higher during the light (sleeping) phase.
- ATP-induced process extension occurred predominantly during the dark (waking) phase and was mediated by P2Y12 receptors.
- P. gingivalis-induced process extension was mediated by P2Y6 receptors, suggesting distinct signaling pathways.
- Bacterial infection may trigger UDP release, leading to neighboring microglial process extension.
Conclusions:
- Microglial response to bacterial brain infection involves process extension, not just retraction.
- Distinct diurnal patterns and receptor mechanisms (P2Y6 for bacteria, P2Y12 for ATP) govern microglial process extension.
- Porphyromonas gingivalis infection initiates a unique microglial surveillance and response pathway.
