title: Beta-glucan activates microglia without inducing cytokine production in Dectin-1-dependent manner.
abstract: Microglia are the resident mononuclear phagocytic cells that are critical for innate and adaptive responses within the CNS. Like other immune cells, microglia recognize and are activated by various pathogen-associated molecular patterns. beta-glucans are pathogen-associated molecular patterns present within fungal cell walls that are known to trigger protective responses in a number of immune cells. In an effort to better understand microglial responses to beta-glucans and the underlying response pathways, we sought to determine whether Dectin-1, a major beta-glucan receptor recently identified in leukocytes, plays a similar role in beta-glucan-induced activation in microglia. In this study, we report that Dectin-1 is indeed expressed on the surface of murine primary microglia, and engagement of the receptor with particulate beta-glucan resulted in an increase in tyrosine phosphorylation of spleen tyrosine kinase, a hallmark feature of the Dectin-1 signaling pathway. Moreover, phagocytosis of beta-glucan particles and subsequent intracellular production of reactive oxygen species were also mediated by Dectin-1. However, unlike in macrophages and dendritic cells, beta-glucan-mediated microglial activation did not result in significant production of cytokines or chemokines; thus, the interaction of microglial Dectin-1 with glucan elicits a unique response. Our results suggest that the Dectin-1 pathway may play an important role in antifungal immunity in the CNS.
authors.affiliation: Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Vaibhav B
authors.initials: VB
authors.lastname: Shah
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Huang
authors.forename: Rohan
authors.initials: R
authors.lastname: Keshwara
authors.forename: Tammy
authors.initials: T
authors.lastname: Ozment-Skelton
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.forename: Lakhu
authors.initials: L
authors.lastname: Keshvara
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D009181:Mycoses / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D010587:Phagocytosis / Q000276:immunology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility; D000072377:Syk Kinase; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics; D015054:Zymosan / Q000494:pharmacology; D047071:beta-Glucans / Q000378:metabolism / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D018925:Chemokines; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011505:Protein-Tyrosine Kinases; D017382:Reactive Oxygen Species; D000072377:Syk Kinase; D051195:Toll-Like Receptor 2; D015054:Zymosan; D047071:beta-Glucans; D000099181:Dectin-1; C493486:Tlr2 protein, mouse; C000606897:Syk protein, mouse