Functional characterization of mannose receptor expressed by immunocompetent mouse microglia
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Heiko Zimmer1, Sigrid Riese, Anne Régnier-Vigouroux
1Department of Neurobiology, University of Heidelberg, Germany.
Abstract:
The mannose receptor is a pattern-recognition receptor involved in innate and adaptive immunity. The receptor is mainly expressed by macrophages and, within the brain, by astrocytes and microglia. This study reports for the first time the effects of two classical proinflammatory (interferon-gamma, IFNgamma) and anti-inflammatory (interleukin-4, IL-4) cytokines on the levels of expression and activity of the mannose receptor expressed by mouse microglia, the brain resident macrophages. As observed for macrophages, IFNgamma treatment led to a decrease and IL-4 to an increase of mannose receptor expression. Consequently, the rates of pinocytosis were strongly upregulated by IL-4 and inhibited by IFNgamma. This latter, however, resumed with time and reached again the constitutive rate of pinocytosis. This recovery resulted from an increased pinocytic activity of the few mannose receptor molecules still expressed by IFNgamma-treated microglia. This may suggest a brain-specific regulation of the effects of IFNgamma since such a phenomenon has not been observed in macrophages. Together, these observations demonstrate that cytokine-stimulated immunocompetent microglia express a functional mannose receptor.
Insights
This study shows that interferon-gamma and interleukin-4 regulate the mannose receptor on mouse microglia. Microglia, the brain
Area of Science:
- Neuroimmunology
- Cellular immunology
Background:
- The mannose receptor (MR) is a pattern-recognition receptor crucial for innate and adaptive immunity.
- MR is expressed by macrophages and in the brain by astrocytes and microglia.
Purpose of the Study:
- To investigate the effects of interferon-gamma (IFNγ) and interleukin-4 (IL-4) on MR expression and activity in mouse microglia.
- To explore potential brain-specific regulatory mechanisms of cytokine effects on microglia.
Main Methods:
- Treatment of mouse microglia with IFNγ and IL-4.
- Quantification of MR expression levels.
- Assessment of pinocytosis rates as a measure of MR activity.
Main Results:
- IFNγ decreased MR expression and inhibited pinocytosis, while IL-4 increased MR expression and upregulated pinocytosis.
- IFNγ-treated microglia showed a recovery of pinocytosis rates despite reduced MR expression, attributed to increased activity of remaining MR molecules.
- This recovery phenomenon was not observed in macrophages, suggesting brain-specific regulation.
Conclusions:
- Cytokine-stimulated microglia express a functional mannose receptor.
- Microglia exhibit unique regulatory responses to IFNγ compared to peripheral macrophages.
- These findings highlight the role of microglia in brain immune responses and potential therapeutic targets.
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