Loss of IL-10 Promotes Differentiation of Microglia to a M1 Phenotype

• Main Authors: Björn Laffer, Dirk Bauer, Susanne Wasmuth, Martin Busch, Tida Viola Jalilvand, Solon Thanos, Gerd Meyer zu Hörste, Karin Loser, Thomas Langmann, Arnd Heiligenhaus, Maren Kasper
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-10-01
• Series: Frontiers in Cellular Neuroscience
• Subjects: cytokines; phenotype; interleukin-10; microglia; M1/2 polarization; lipopolysaccharide
• Online Access: https://www.frontiersin.org/article/10.3389/fncel.2019.00430/full

Microglia represent the primary resident immune cells of the central nervous system (CNS) and modulate local immune responses. Depending on their physiological functions, microglia can be classified into pro- (M1) and anti-inflammatory (M2) phenotype. Interleukin (IL)-10 is an important modulator of neuronal homeostasis, with anti-inflammatory and neuroprotective functions, and can be released by microglia. Here, we investigated how IL-10 deficiency affected the M1/2 polarization of primary microglia upon lipopolysaccharide (LPS) stimulation in vitro. Microglia phenotypes were analyzed via flow cytometry. Cytokine and chemokine secretion were examined by ELISA and bead-based multiplex LEGENDplexTM. Our results showed that genetic depletion of IL-10 led to elevated M1 like phenotype (CD86+ CD206−) under pro-inflammatory conditions associated with increased frequency of IL-6+, TNF-α+ cells and enhanced release of several pro-inflammatory chemokines. Absence of IL-10 led to an attenuated M2 like phenotype (CD86− CD206+) and a reduced secretion of TGF-β1 upon LPS stimulation. In conclusion, IL-10 deficiency may promote the polarization of microglia into M1-prone phenotype under pro-inflammatory conditions.