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Updated: Apr 30, 2026
An Engulfment Assay: A Protocol to Assess Interactions Between CNS Phagocytes and Neurons
Published on: June 8, 2014
Astrocyte-derived complement C3 facilitated microglial phagocytosis of synapses in Staphylococcus aureus-associated
Haifang Zhang1,2, Qiyuan Jin1, Jijie Li1
1Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Abstract:
The presence of pathogens is a significant challenge in causing brain infections and tissue damage. There is growing evidence that pathogen infections are commonly associated with cognitive dysfunction and mental health problems, but the underlying mechanisms are not yet fully understood. Here, we found microglia and astrocyte activation, neuronal damage, synapse loss, and cognitive impairment in a Staphylococcus aureus (S. aureus) induced mouse model. An unbiased transcription profile of isolated microglia derived from S. aureus-infected mice identified the involvement of microglial phagosome and regulation of neurogenesis. Our findings indicate that the complement C1q and C3 are upregulated, and astroglial release of C3 activates microglia to phagocytose synapses. Blocking the C3-C3aR axis can improve microglial phagocytosis, thus rescuing synapse loss and cognitive impairment in infected mice. These results indicate that S. aureus induces synapse elimination and cognitive impairment by activating microglia and astrocytes through C3-C3aR signaling. This suggests a mechanism of complement signaling bridged crosstalk between astrocyte and microglia in the S. aureus-associated post-infectious synapse loss and cognitive dysfunction, and provide potential therapeutic targets for managing pathogen-associated brain infections.
Insights
Staphylococcus aureus brain infections cause cognitive impairment by activating microglia and astrocytes. Blocking complement C3 signaling can prevent synapse loss and improve cognitive function, offering therapeutic targets for brain infections.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Pathogen-induced brain infections can lead to neuronal damage and cognitive dysfunction.
- The precise mechanisms linking infections to neurological deficits, particularly synapse loss, remain unclear.
Purpose of the Study:
- To investigate the role of microglia and astrocytes in Staphylococcus aureus-induced cognitive impairment.
- To elucidate the signaling pathways involved in synapse loss during S. aureus brain infections.
Main Methods:
- Establishment of a Staphylococcus aureus mouse model to study brain infection.
- Transcriptional profiling of microglia to identify molecular pathways.
- Analysis of complement system involvement, specifically C1q and C3.
- Assessment of synapse loss and cognitive function following C3-C3aR axis blockade.
Main Results:
- S. aureus infection induced microglia and astrocyte activation, neuronal damage, synapse loss, and cognitive impairment.
- Microglia displayed altered phagosome activity and neurogenesis regulation.
- Complement C3, released by astrocytes, was found to activate microglia, leading to synapse phagocytosis.
- Blocking the C3-C3aR axis mitigated microglial phagocytosis, preserved synapses, and rescued cognitive deficits.
Conclusions:
- S. aureus triggers synapse elimination and cognitive impairment via C3-C3aR-mediated crosstalk between astrocytes and microglia.
- This study reveals a complement-driven mechanism underlying post-infectious synapse loss and cognitive dysfunction.
- Targeting the C3-C3aR pathway presents a potential therapeutic strategy for managing S. aureus-associated neurological complications.
