Complement Receptor Type 3 Mediates Phagocytosis and Killing ofListeria monocytogenesby a TNF-α- and IFN-γ- Stimulated Macrophage Precursor Hybrid

Previous work demonstrated that engagement of complement receptor type 3 (CR3) was required for inflammatory peritoneal macrophages to phagocytose and kill the facultative intracellular bacteriumListeria monocytogenes.The experiments described here tested the role of CR3 in phagocytosis and killing ofListeriaby a clonal population of TNF-α/IFN-γ-stimulated macrophage precursor hybrids. Stimulation with TNF-α and IFN-γ increased CR3 expression 20-fold and induced a big increase in phagocytic activity. Phagocytosis and killing ofListeriaby these cells were inhibited when bacteria were opsonized with complement-depleted serum or by incubation of the macrophages with anti-CR3 mAb. Furthermore, cytokine-stimulated macrophages could not killListeriaopsonized with heat-inactivated anti-Listeriaantiserum, indicating that macrophage receptors which mediate phagocytosis do not necessarily promote bactericidal activity. These data suggest that upregulation of CR3 and CR3-mediated phagocytosis are mechanisms by which TNF-α and IFN-γ stimulate nonphagocytic, nonbactericidal macrophage precursors to kill intracellular bacterial pathogens.