A monoclonal antibody directed against the murine macrophage surface molecule F4/80 modulates natural immune response to Listeria monocytogenes.
Whole spleen cell cultures from SCID mice release high levels of IFN-gamma when exposed to heat-killed Listeria monocytogenes (HKL). This microbe-induced and T cell-independent response depends on both macrophages (MPhi) and NK cells: HKL-stimulated MPhi release TNF-alpha and IL-12, which together activate NK cells for IFN-gamma release. We show here that this cytokine-mediated activation cascade can be modulated by a mAb against the MPhi surface glycoprotein F4/80. HKL-induced IL-12, TNF-alpha, and IFN-gamma in SCID whole spleen cell cultures was inhibited by coincubation with anti-F4/80 mAb whereas IL-1 and IL-10 were enhanced. Both effects were apparent at mRNA and protein release levels. Whereas inhibitory activities were F4/80 Ag specific, stimulatory effects were Fc dependent and nonspecific. Furthermore, cytokine inhibition by anti-F4/80 was only apparent when MPhi and NK cells were present simultaneously and in close vicinity, indicating that direct cell-to-cell contact is a prerequisite. These data suggest a novel pathway for microbe-induced MPhi/NK cell interaction involving direct cell-to-cell signaling and give the first evidence for a functional role of the MPhi surface glycoprotein F4/80.
Warschkau
H
H
Department of Immunology, Robert Koch Institute, Berlin, Germany.
Kiderlen
A F
AF
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D000918:Antibody Specificity; D000943:Antigens, Differentiation / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003260:Contact Inhibition / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000939:Epitopes / Q000502:physiology; D005260:Female; D006358:Hot Temperature; D007113:Immunity, Innate / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007700:Kinetics; D008089:Listeria monocytogenes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D016207:Cytokines; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; C036763:monocyte-macrophage differentiation antigen; D007371:Interferon-gamma