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Updated: Dec 14, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Gasdermin-D-dependent IL-1α release from microglia promotes protective immunity during chronic Toxoplasma gondii
Samantha J Batista1, Katherine M Still1, David Johanson1
1Center for Brain Immunology and Glia, Department of Neuroscience, University of Virginia, Charlottesville, VA, 22908, USA.
Abstract:
Microglia, resident immune cells of the CNS, are thought to defend against infections. Toxoplasma gondii is an opportunistic infection that can cause severe neurological disease. Here we report that during T. gondii infection a strong NF-κB and inflammatory cytokine transcriptional signature is overrepresented in blood-derived macrophages versus microglia. Interestingly, IL-1α is enriched in microglia and IL-1β in macrophages. We find that mice lacking IL-1R1 or IL-1α, but not IL-1β, have impaired parasite control and immune cell infiltration within the brain. Further, we show that microglia, not peripheral myeloid cells, release IL-1α ex vivo. Finally, we show that ex vivo IL-1α release is gasdermin-D dependent, and that gasdermin-D and caspase-1/11 deficient mice show deficits in brain inflammation and parasite control. These results demonstrate that microglia and macrophages are differently equipped to propagate inflammation, and that in chronic T. gondii infection, microglia can release the alarmin IL-1α, promoting neuroinflammation and parasite control.
Insights
Microglia release the alarmin IL-1α during Toxoplasma gondii infection, promoting neuroinflammation and parasite control. This highlights distinct roles for microglia and macrophages in brain immunity.
Area of Science:
- Neuroimmunology
- Infectious Disease
Background:
- Microglia are the primary immune cells in the central nervous system (CNS).
- Toxoplasma gondii infection can lead to severe neurological complications.
Purpose of the Study:
- To investigate the distinct inflammatory responses of microglia and blood-derived macrophages during Toxoplasma gondii infection.
- To elucidate the role of IL-1α and IL-1β in neuroinflammation and parasite control.
Main Methods:
- Transcriptional profiling of microglia and macrophages.
- Analysis of knockout mice (IL-1R1, IL-1α, IL-1β, gasdermin-D, caspase-1/11).
- Ex vivo cytokine release assays.
Main Results:
- Microglia and macrophages exhibit differential inflammatory signatures, with IL-1α enriched in microglia and IL-1β in macrophages.
- Mice lacking IL-1R1 or IL-1α show impaired parasite control and reduced immune cell infiltration.
- Microglia, but not peripheral myeloid cells, release IL-1α ex vivo in a gasdermin-D dependent manner.
- Gasdermin-D and caspase-1/11 deficient mice exhibit reduced brain inflammation and parasite control.
Conclusions:
- Microglia and macrophages possess distinct inflammatory capabilities.
- Microglia-derived IL-1α plays a crucial role in promoting neuroinflammation and controlling T. gondii infection.
- Gasdermin-D-mediated IL-1α release by microglia is critical for host defense against chronic T. gondii infection.
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