Inhibition of Dectin-1 Ameliorates Neuroinflammation by Regulating Microglia/Macrophage Phenotype After Intracerebral Hemorrhage in Mice.

Polarization of microglia/macrophages toward the pro-inflammatory phenotype is an important contributor to neuroinflammation after intracerebral hemorrhage (ICH). Dectin-1 is a pattern recognition receptor that has been reported to play a key role in regulating neuroinflammation in ischemic stroke and spinal cord injury. However, the role and mechanism of action of Dectin-1 after ICH remains unclear. In this study, we investigated the effect of Dectin-1 on modulating the microglia/macrophage phenotype and neuroinflammation and the possible underlying mechanism after ICH. We found that Dectin-1 expression increased after ICH, and was mainly localized in microglia/macrophages. Neutrophil infiltration and microglia/macrophage polarization toward the pro-inflammatory phenotype increased after ICH. However, treatment with a Dectin-1 inhibitor reversed these phenomena and induced a shift the anti-inflammatory phenotype in microglia/macrophages; this resulted in alleviation of neurological dysfunction and facilitated hematoma clearance after ICH. We also found that Dectin-1 crosstalks with the downstream pro-inflammatory pathway, Card9/NF-κB, by activating spleen tyrosine kinase (Syk) both in vivo and in vitro. In conclusion, our data suggest that Dectin-1 is involved in the microglia/macrophage polarization and functional recovery after ICH, and that this mechanism, at least in part, may contribute to the involvement of the Syk/Card9/NF-kB pathway.