Dissimilar and similar functional properties of complement receptor-3 in microglia and macrophages in combating yeast pathogens by phagocytosis.
Central nervous system (CNS) microglia (MG) and peripheral tissue macrophages (MO) remove pathogens by phagocytosis. Zymosan, a model yeast pathogen, is a beta-glucan rich particle that readily activates the complement system and then becomes C3bi-opsonized (op). Complement receptor-3 (CR3) has initially been implicated in mediating the phagocytosis of both C3bi-op and non-opsonized (nop) zymosan by MO through C3bi and beta-glucan binding sites, respectively. Later, the role of CR3 as a phagocytic beta-glucan receptor has been questioned and the supremacy of beta-glucan receptor Dectin-1 advocated. We compare here between primary mouse CNS MG and peripheral tissue MO with respect to CR3 and Dectin-1 mediated phagocytosis of C3bi-op and nop zymosan. We report that MG and MO display similar as well as dissimilar functional properties in this respect. Although CR3 and Dectin-1 function both as beta-glucan/non-opsonic receptors in MG during nop zymosan phagocytosis, Dectin-1, but not CR3, does so in MO. CR3 functions also as a C3bi/opsonic receptor in MG and MO during C3bi-op zymosan phagocytosis, leading to phagocytosis which is more efficient than that of nop zymosan. Dectin-1 contributes, albeit less than CR3, to phagocytosis of C3bi-op zymosan in MG and further less in MO, suggesting that C3bi-opsonization does not block all beta-glucan sites on zymosan from binding Dectin-1 on phagocytes. Thus, altogether CR3 and Dectin-1 contribute both to phagocytosis of nop and C3bi-op zymosan in MG, whereas MO switch from CR3-independent/Dectin-1-dependent phagocytosis of nop zymosan to phagocytosis of C3bi-op zymosan where CR3 dominates over Dectin-1.
Hadas
Smadar
S
Department of Medical Neurobiology, IMRIC, Hebrew University Hadassah Medical School and the Eric Roland Center for Neurodegenerative Diseases, Jerusalem, Israel.
Reichert
Fanny
F
Rotshenker
Shlomo
S
D000818:Animals; D001665:Binding Sites / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020314:Central Nervous System Fungal Infections / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009895:Opsonin Proteins / Q000378:metabolism; D017933:Peripheral Nervous System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D015054:Zymosan / Q000378:metabolism; D000099181:Dectin-1
D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009895:Opsonin Proteins; D015054:Zymosan; D000099181:Dectin-1