Beta-Glucan Activates Microglia Through Dectin-1 Without Inducing Cytokine Production

Microglia, the resident mononuclear phagocytic cells, are critical for immune responses within the CNS. They recognize and are activated by various Pathogen Associated Molecular Patterns (PAMPs). β‐glucans are PAMPs present within fungal cell walls that are known to trigger protective responses in a number of immune cells. To better understand microglial responses to β‐glucans and the underlying signaling pathways, we sought to determine if Dectin‐1, a major β‐glucan receptor recently identified in leukocytes, mediates β‐glucan induced activation of microglia. Here, we report that Dectin‐1 is expressed on the surface of murine primary microglia, and engagement of the receptor with particulate β‐glucan resulted in an increase in tyrosine phosphorylation of Syk, a hallmark feature of the Dectin‐1 signaling pathway. Moreover, phagocytosis of β‐glucan particles and subsequent intracellular production of ROS were also mediated by Dectin‐1. Further, interaction of β‐glucan with Dectin‐1 resulted in activation of Vav and PI3K/Akt pathways, suggesting that β‐glucan induce multiple signaling pathways in microglia. However, unlike in leukocytes, β‐glucan mediated microglial activation did not result in production of cytokines. Thus, the interaction of microglial Dectin‐1 with glucan elicits a unique response, suggesting that the Dectin‐1 pathway may play an important role in antifungal immunity in the CNS.