Complement receptor type 3 (CD11b/CD18) involvement is essential for killing of Listeria monocytogenes by mouse macrophages.
Recent work indicated that C receptor type 3 (CR3) mediates most phagocytosis of the facultative intracellular bacterium Listeria monocytogenes by mouse macrophages, which can kill it. In contrast, phagocytosis of Listeria by a population of nonlistericidal macrophages was largely CR3-independent. These findings suggested that CR3 binding during phagocytosis may be important in determining whether a macrophage kills Listeria, or is parasitized by the bacterium. The experiments reported here tested this hypothesis. When phagocytosis and killing were assayed separately, normally listericidal peritoneal macrophages still could phagocytose to some extent, but lost listericidal activity when CR3 was blocked by mAb. Anti-CR3 mAb inhibited killing in a dose-dependent fashion, and at high doses the cells became permissive hosts. Microbicidal function also was inhibited when active C components were absent during phagocytosis and during killing. Because Listeria are confined to phagosomes in listericidal macrophages but escape into the cytoplasm in nonlistericidal macrophages, we tested whether anti-CR3 mAb enhanced phagosomal escape. In fact, escape of Listeria into the cytoplasm was rare in both control and anti-CR3 mAb-treated macrophages. Moreover, electron microscopy of these cells demonstrated dividing intraphagosomal bacteria. Taken together, these results suggest that binding to CR3 during phagocytosis leads to bacterial killing, and that phagocytic pathways engaged when binding to CR3 is blocked do not trigger microbicidal activity. Furthermore, restriction of Listeria to the phagosome in the absence of CR3 engagement is not by itself sufficient for macrophage listericidal activity.
Drevets
D A
DA
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Leenen
P J
PJ
Campbell
P A
PA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010587:Phagocytosis
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen