IgM-Dependent Phagocytosis in Microglia Is Mediated by Complement Receptor 3, Not Fcα/μ Receptor.
IgM-Dependent Phagocytosis in Microglia Is Mediated by Complement Receptor 3, Not Fcα/μ Receptor.
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小胶质细胞中IgM依赖性吞噬作用是由补体受体3介导的，而不是FCα/μ受体。
DOI：
10.4049/jimmunol.1401195
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发表时间：
2015-12-01
期刊：
影响因子：
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通讯作者：
Möller T
中科院分区：
文献类型：
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作者：
Weinstein JR;Quan Y;Hanson JF;Colonna L;Iorga M;Honda S;Shibuya K;Shibuya A;Elkon KB;Möller T
小胶质细胞在中枢神经系统受体介导的吞噬作用中发挥重要作用。在脑脓肿和其他中枢神经系统感染中，侵入的细菌经历免疫球蛋白（IG）或补体的调理作用。小胶质细胞通过Fc或补体受体识别这些调理的病原体，触发吞噬作用。在此，我们研究了Fcα/μ受体（Fcα/μR）在小胶质细胞吞噬作用中的作用，Fc α/μR是研究较少的IgM和伊加受体。我们发现，原代小胶质细胞以及N9小胶质细胞表达Fcα/μR。我们还发现，抗金黄色葡萄球菌（SA）IgM显着增加小胶质细胞SA吞噬率。为了明确检测Fcα/μR在IgM介导的吞噬作用中的作用，我们在Fcα/μR-/-小鼠的小胶质细胞中进行了实验。令人惊讶的是，我们发现SA的IgM依赖性吞噬作用在来自野生型（WT）或Fcα/μR-/-小鼠的小胶质细胞中相似。我们推测补体受体的IgM依赖性激活可能有助于IgM介导的吞噬作用的增加。为了测试这一点，我们使用了补体受体3（CR 3）组分（CD 11b和CD 18）以及补体因子3（C3）的免疫学和遗传学灭活。与抗CD 11b阻断抗体预孵育后，WT小胶质细胞和巨噬细胞中IgM介导的SA吞噬作用降低，但IgG介导的SA吞噬作用未降低。在来自CD 18-/-和C3-/-小鼠的小胶质细胞中，SA的IgM依赖性吞噬作用也降低。综上所述，我们的研究结果表明CR 3和C3，而不是Fcα/μR，参与了小胶质细胞对SA的IgM介导的吞噬作用。
Microglia play an important role in receptor-mediated phagocytosis in the CNS. In brain abscess and other CNS infections, invading bacteria undergo opsonization with immunoglobulins (Ig) or complement. Microglia recognize these opsonized pathogens by Fc or complement receptors triggering phagocytosis. Here we investigated the role of Fcα/μ receptor (Fcα/μR), the less studied receptor for IgM and IgA, in microglial phagocytosis. We showed that primary microglia, as well as N9 microglial cells, express Fcα/μR. We also showed that anti-Staphylococcus aureus (SA) IgM markedly increased the rate of microglial SA phagocytosis. To unequivocally test the role of Fcα/μR in IgM-mediated phagocytosis we performed experiments in microglia from Fcα/μR-/- mice. Surprisingly, we found that IgM-dependent phagocytosis of SA was similar in microglia derived from wild-type (WT) or Fcα/μR-/- mice. We hypothesized that IgM-dependent activation of complement receptors might contribute to the IgM-mediated increase in phagocytosis. To test this we used immunologic and genetic inactivation of complement receptor 3 (CR3) components (CD11b and CD18) as well as complement factor-3 (C3). IgM-, but not IgG-, mediated phagocytosis of SA was reduced in WT microglia and macrophages following pre-incubation with an anti-CD11b blocking antibody. IgM-dependent phagocytosis of SA was also reduced in microglia derived from CD18-/- and C3-/- mice. Taken together, our findings implicate CR3 and C3, but not Fcα/μR, in IgM-mediated phagocytosis of SA by microglia.