title: Regulation of Fcgamma receptors and immunoglobulin G-mediated phagocytosis in mouse microglia.
abstract: 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.
authors.affiliation: Department of Neurology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Quan
authors.forename: Thomas
authors.initials: T
authors.lastname: Möller
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Weinstein
mesh_terms: 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
chemical_list: D007074:Immunoglobulin G; D018793:Interleukin-13; D012333:RNA, Messenger; D017452:Receptors, IgG; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
references.citation: J Neuroinflammation. 2007 Mar 20;4:10
references.pmid: 17374157
references.citation: J Neurosci. 1986 Aug;6(8):2163-78
references.pmid: 3018187
references.citation: Nat Neurosci. 2007 Nov;10(11):1387-94
references.pmid: 17965659
references.citation: Nat Med. 2000 Aug;6(8):916-9
references.pmid: 10932230
references.citation: Nat Rev Immunol. 2003 Jan;3(1):23-35
references.pmid: 12511873
references.citation: Glia. 2008 Feb;56(3):271-83
references.pmid: 18069669
references.citation: J Exp Med. 2007 Jun 11;204(6):1359-69
references.pmid: 17502666
references.citation: J Neurosci. 2006 Dec 13;26(50):12904-13
references.pmid: 17167081
references.citation: Immunity. 2002 Mar;16(3):379-89
references.pmid: 11911823
references.citation: J Clin Invest. 2005 Oct;115(10):2914-23
references.pmid: 16167082
references.citation: Annu Rev Immunol. 1997;15:563-91
references.pmid: 9143700
references.citation: Annu Rev Immunol. 2001;19:275-90
references.pmid: 11244038
references.citation: J Immunol. 2001 Jan 1;166(1):531-7
references.pmid: 11123333
references.citation: J Biol Chem. 2002 Feb 15;277(7):5082-9
references.pmid: 11741917
references.citation: Science. 2005 Jan 28;307(5709):590-3
references.pmid: 15681388
references.citation: Annu Rev Immunol. 1999;17:701-38
references.pmid: 10358772
references.citation: Cell Mol Life Sci. 2008 Jul;65(13):1957-76
references.pmid: 18322649
references.citation: J Neurochem. 2006 Nov;99(4):1176-87
references.pmid: 17018025
references.citation: J Neurosci. 2007 Oct 3;27(40):10714-21
references.pmid: 17913905
references.citation: Science. 1986 Nov 7;234(4777):718-25
references.pmid: 2946078
references.citation: Neuroreport. 1997 Dec 22;8(18):3851-6
references.pmid: 9462454
references.citation: Adv Immunol. 1994;57:1-127
references.pmid: 7872156
references.citation: J Neuroimmune Pharmacol. 2006 Jun;1(2):127-37
references.pmid: 18040779
references.citation: Glia. 2002 Nov;40(2):133-9
references.pmid: 12379901
references.citation: J Neurochem. 2000 Oct;75(4):1539-47
references.pmid: 10987834
references.citation: J Neurochem. 1986 Sep;47(3):779-89
references.pmid: 3734801
references.citation: Nihon Rinsho. 2003 Aug;61(8):1428-34
references.pmid: 12962034
references.citation: J Neurosci. 2000 May 15;20(10):3612-21
references.pmid: 10804203
references.citation: Neurochem Res. 2009 Mar;34(3):445-52
references.pmid: 18686031
references.citation: Neurodegener Dis. 2008;5(1):8-15
references.pmid: 18075269
references.citation: J Immunol. 2002 Sep 1;169(5):2264-73
references.pmid: 12193691
references.citation: J Exp Med. 1999 Jan 4;189(1):179-85
references.pmid: 9874574
references.citation: Am J Pathol. 2006 May;168(5):1464-73
references.pmid: 16651614
references.citation: J Neurochem. 1995 Jan;64(1):121-9
references.pmid: 7798905
references.citation: Nat Rev Immunol. 2007 Dec;7(12):964-74
references.pmid: 18037898
references.citation: Annu Rev Immunol. 1989;7:145-73
references.pmid: 2523712
references.citation: New Microbiol. 2006 Jul;29(3):193-9
references.pmid: 17058786
references.citation: Nat Rev Immunol. 2008 Jul;8(7):533-44
references.pmid: 18551128