Regulation of Fcgamma receptors and immunoglobulin G-mediated phagocytosis in mouse microglia.
As resident macrophages in the CNS, microglia can transform from a surveillance state to an activated phenotype in response to brain injury. During this transition microglia become highly capable phagocytic cells. Invading pathogens undergo opsonization with immunoglobulins and microglia recognize these opsonized pathogens through interaction with their cognate F(c) receptors. In mice, both FcgammaRI and FcgammaRIIb receptors are involved in IgG-mediated phagocytosis of opsonzied pathogens. At sites of inflammation, microglial activity is regulated by T-cell derived cytokines. Here we first investigated the effects of IFN-gamma, IL-4, IL-13 and GM-CSF on expression of FcgammaRI and FcgammaRIIb mRNA levels in both primary microglia and microglial cell line N9. Using quantitative real-time PCR we show that IFN-gamma induced a 4-fold increase in the mRNA level of FcgammaRI but did not induce changes in FcgammaRIIb expression. IL-4 and IL-13 induced approximately 2-fold increases in expression of FcgammaRIIb mRNA, but had no effect on FcgammaRI expression. GM-CSF increased both FcgammaRI and FcgammaRIIb mRNA expression. We then characterized the ability of these same cytokines to regulate phagocytosis of immune complexes composed of IgG and the bacteria Staphylococcus aureus. IFN-gamma and GM-CSF both induced approximately 2-fold increases in IgG-mediated phagocytosis whereas IL-4 and IL-13 both decreased IgG-mediated phagocytosis by about one-third. None of the cytokines influenced basal levels of phagocytosis. These findings demonstrate a highly selective cytokine-induced regulation of both phagocytosis-related Fcgamma receptor subtypes and IgG-mediated phagocytosis itself in microglia. This selective regulation has implications for our understanding of the pathophysiology of CNS infection and autoimmune disease.
Quan
Yi
Y
Department of Neurology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Möller
Thomas
T
Weinstein
Jonathan R
JR
D000818:Animals; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007074:Immunoglobulin G / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D010587:Phagocytosis; D012333:RNA, Messenger / Q000096:biosynthesis; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics; D013211:Staphylococcus aureus / Q000502:physiology
D007074:Immunoglobulin G; D018793:Interleukin-13; D012333:RNA, Messenger; D017452:Receptors, IgG; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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