Journal
JOURNAL OF IMMUNOLOGY
Volume 195, Issue 11, Pages 5309-5317Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1401195
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Funding
- American Heart Association [0750078Z]
- National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [F32AR065837]
- National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS065008]
- Grants-in-Aid for Scientific Research [26670185, 26670575, 15H01365, 15K15659, 25293091, 26293383] Funding Source: KAKEN
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Microglia play an important role in receptor-mediated phagocytosis in the CNS. In brain abscess and other CNS infections, invading bacteria undergo opsonization with Igs or complement. Microglia recognize these opsonized pathogens by Fc or complement receptors triggering phagocytosis. In this study, we investigated the role of Fc alpha/mu R, the less-studied receptor for IgM and IgA, in microglial phagocytosis. We showed that primary microglia, as well as N9 microglial cells, express Fc alpha/mu R. We also showed that anti-Staphylococcus aureus IgM markedly increased the rate of microglial S. aureus phagocytosis. To unequivocally test the role of Fc alpha/mu R in IgM-mediated phagocytosis, we performed experiments in microglia from Fc alpha/mu R-/- mice. Surprisingly, we found that IgM-dependent phagocytosis of S. aureus was similar in microglia derived from wild-type or Fc alpha/mu R-/- 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 components (CD11b and CD18) as well as C3. IgM-, but not IgG-mediated phagocytosis of S. aureus was reduced in wild-type microglia and macrophages following preincubation with an anti-CD11b blocking Ab. IgM-dependent phagocytosis of S. aureus was also reduced in microglia derived from CD18(-/-) and C3(-/-) mice. Taken together, our findings implicate complement receptor 3 and C3, but not Fc alpha/mu R, in IgMmediated phagocytosis of S. aureus by microglia.
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