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Comparison of polarization properties of human adult microglia and blood-derived macrophages
Bryce A Durafourt1, Craig S Moore, Domenick A Zammit
1Neuroimmunology Unit, Montréal Neurological Institute, McGill University, Montréal, Québec, Canada.
Abstract:
Both microglia, the resident myeloid cells of the CNS parenchyma, and infiltrating blood-derived macrophages participate in inflammatory responses in the CNS. Macrophages can be polarized into M1 and M2 phenotypes, which have been linked to functional properties including production of inflammation association molecules and phagocytic activity. We compare phenotypic and functional properties of microglia derived from the adult human CNS with macrophages derived from peripheral blood monocytes in response to M1 and M2 polarizing conditions. Under M1 conditions, microglia and macrophages upregulate expression of CCR7 and CD80. M2 treatment of microglia-induced expression of CD209 but not additional markers CD23, CD163, and CD206 expressed by M2 macrophages. M1-polarizing conditions induced production of IL-12p40 by both microglia and macrophages; microglia produced higher levels of IL-10 under M1 conditions than did macrophages. Under M2 conditions, microglia ± LPS produced comparable levels of IL-10 under M1 conditions whereas IL-10 was induced by LPS in M2 macrophages. Myelin phagocytosis was greater in microglia than macrophages under all conditions; for both cell types, activity was higher for M2 cells. Our findings delineate distinctive properties of microglia compared with exogenous myeloid cells in response to signals derived from an inflammatory environment in the CNS.
Insights
Human microglia and blood-derived macrophages exhibit distinct responses to inflammation. Microglia show unique M2 polarization markers and greater myelin phagocytosis, highlighting their specialized role in the central nervous system (CNS).
Area of Science:
- Neuroimmunology
- Cellular Biology
Background:
- Microglia (resident CNS myeloid cells) and blood-derived macrophages are key players in CNS inflammation.
- Macrophages polarize into M1 (pro-inflammatory) and M2 (anti-inflammatory/phagocytic) phenotypes with distinct functions.
Purpose of the Study:
- To compare the phenotypic and functional differences between human microglia and peripheral blood-derived macrophages.
- To investigate their responses to M1 and M2 polarizing conditions.
Main Methods:
- Human microglia and monocyte-derived macrophages were subjected to M1 and M2 polarizing stimuli.
- Phenotypic markers (CCR7, CD80, CD209, CD23, CD163, CD206) and cytokine production (IL-12p40, IL-10) were analyzed.
- Myelin phagocytosis assays were performed.
Main Results:
- Both cell types upregulated CCR7 and CD80 under M1 conditions.
- Microglia expressed CD209 under M2 conditions, unlike macrophages which expressed additional M2 markers.
- Microglia produced higher IL-10 levels under M1 conditions than macrophages.
- Myelin phagocytosis was higher in microglia than macrophages, and enhanced in M2-polarized cells for both types.
Conclusions:
- Human microglia possess distinct phenotypic and functional properties compared to blood-derived macrophages.
- These differences underscore the specialized role of microglia in responding to CNS inflammatory environments.
