Dectin‐1 mediates zymosan responses in microglia

Microglia are the major immune component of brain that play a central role in neuroinflammation. Microglia are normally quiescent but are rapidly activated in response to pathogens as well as physical, chemical, or ischemic injuries. Zymosan, a β‐glucan‐containing particle derived from yeast cell wall, is commonly used to activate microglia in experimental models of neuroinflammation, although the identity of its receptor remains unclear. Dectin‐1, a transmembrane lectin, has recently emerged as the major β‐glucan receptor in leukocytes. For example, in macrophages, Dectin‐1 mediates zymosan‐induced phagocytic activity and secretion of pro‐inflammatory cytokines in collaboration with Toll‐like Receptor‐2. Given the hematopoietic cell lineage of microglia, we asked whether Dectin‐1 could play a similar role in zymosan‐dependent microglial activation. Here, we report that Dectin‐1 is indeed expressed in the brain by microglia, and in vitro zymosan stimulation of microglia resulted in tyrosine phosphorylation of Syk, an immediate downstream component of the Dectin‐1 signaling pathway. Furthermore, both Dectin‐1 and Syk phosphorylation were required for zymosan phagocytosis by microglia, but unlike in leukocytes zymosan‐induced secretion of cytokines/chemokines occurred independently of Dectin‐1. Thus, we show for the first time the presence of functional Dectin‐1/Syk pathway in microglia.