Inflammasome-Induced IL-1β Secretion in Microglia Is Characterized by Delayed Kinetics and Is Only Partially Dependent on Inflammatory Caspases
Open accessAbstract
Inflammasomes are multiprotein complexes that link pathogen recognition and cellular stress to the processing of the proinflammatory cytokine interleukin-1β (IL-1β). Whereas inflammasome-mediated activation is heavily studied in hematopoietic macrophages and dendritic cells, much less is known about microglia, resident tissue macrophages of the brain that originate from a distinct progenitor. To directly compare inflammasome-mediated activation in different types of macrophages, we isolated primary microglia and hematopoietic macrophages from adult, healthy rhesus macaques. We analyzed the expression profile of NOD (nucleotide-binding oligomerization domain)-like receptors, adaptor proteins, and caspases and characterized inflammasome activation and regulation in detail. We here demonstrate that primary microglia can respond to the same innate stimuli as hematopoietic macrophages. However, microglial responses are more persistent due to lack of negative regulation on pro-IL-1β expression. In addition, we show that while caspase 1, 4, and 5 activation is pivotal for inflammasome-induced IL-1β secretion by hematopoietic macrophages, microglial secretion of IL-1β is only partially dependent on these inflammatory caspases. These results identify key cell type-specific differences that may aid the development of strategies to modulate innate immune responses in the brain.
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The action of TET2 is highly context-specific, with fundamental differences in the regulation of innate immune responses between peripheral immune cells (and specifically monocyte-derived macrophages) and microglia.
“This effect differs from the result reported here and highlights fundamental differences in the regulation of the innate immune responses between peripheral immune cells (and specifically monocyte-derived macrophages) and microglia (Burm et al., 2015) (London et al., 2013; Zarruk et al., 2018), suggesting that the action of TET2 is highly context-specific.”
From TET2 Regulates the Neuroinflammatory Response in Microglia (2019) · cites this paper as Burm et al., 2015
IL-1β activation is not strictly caspase-1 dependent in primary microglia, suggesting that inflammasomes may not be necessary for the processing of IL-1β into its mature form in this CNS innate immune cell.
“Burm et al (2015) have recently demonstrated that IL-1β activation is not strictly caspase-1 dependent in primary microglia, suggesting that inflammasomes may not be necessary for the processing of IL-1β into its mature form in this CNS innate immune cell.”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Burm et al, 2015
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- Authors
- Burm, S. M., Zuiderwijk-Sick, E. A., ‘t Jong, A. E. J., van der Putten, C., Veth, J., Kondova, I., & Bajramovic, J. J.
- Affiliations
- Biomedical Primate Research Centre (NL)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-01-14
- Volume
- 35
- Issue
- 2
- Pages
- 678-687
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6605364
- OpenAlex
- W2020008646
- Cited by
- 82
- References
- 61
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 4 · 2022: 11 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 8 · 2017: 11 · 2016: 9 · 2015: 2
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- inflammasome, interleukin-1β secretion, microglia, NOD-like receptors, caspase-1, caspase-4, caspase-5, rhesus monkeys
- MeSH terms
- Animals, Cells, Cultured, Female, Kinetics, Macaca mulatta, Macrophages, Male, Reaction Time, Microglia, Caspases, Nod2 Signaling Adaptor Protein, Nod1 Signaling Adaptor Protein, Interleukin-1beta, Inflammasomes
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