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-indu ced and T cell-independent response depends on both macrophages (M Phi) and NK cells: HKL-stimulated M Phi release TNF-alpha and IL-12, which together activate NK cells for IFN-gamma release. We show here that this cytokine-m ediated activation cascade can be modulated by a mAb against the M Phi, sur face glycoprotein F4/80. HKL-induced IL-12, TNF-alpha, and IFN-gamma in SCI D 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 mRN A and protein release levels. Whereas inhibitory activities were F4/80 Ag s pecific, stimulatory effects were Fc dependent and nonspecific. Furthermore , cytokine inhibition by anti-F4/80 was only apparent when M Phi, and NK ce lls were present simultaneously and in close vicinity, indicating that dire ct cell-to-cell contact is a prerequisite. These data suggest a novel pathw ay for microbe-induced M Phi/NK cell interaction involving direct cell-to-c ell signaling and give the first evidence for a functional role of the M Ph i, surface glycoprotein F4/80.