Beta-glucan activates microglia without inducing cytokine production in Dectin-1-dependent manner.
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.
Shah
Vaibhav B
VB
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.
Huang
Yongcheng
Y
Keshwara
Rohan
R
Ozment-Skelton
Tammy
T
Williams
David L
DL
Keshvara
Lakhu
L
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
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