CapG−/− Mice Have Specific Host Defense Defects That Render Them More Susceptible than CapG+/+ Mice to Listeria monocytogenes Infection but Not to Salmonella enterica Serovar Typhimurium Infection

摘要

Loss of the actin filament capping protein CapG has no apparent effect on the phenotype of mice maintained under sterile conditions; however, bone marrow-derived macrophages from CapG−/− mice exhibited distinct motility defects. We examined the ability of CapG−/− mice to clear two intracellular bacteria, Listeria monocytogenes and Salmonella enterica serovar Typhimurium. The 50% lethal dose of Listeria was 10-fold lower for CapG−/− mice than for CapG+/+ mice (6 × 103 CFU for CapG−/− mice and 6 × 104 CFU for CapG+/+ mice), while no difference was observed for Salmonella. The numbers of Listeria cells in the spleens and livers were significantly higher in CapG−/− mice than in CapG+/+ mice at days 5 to 9, while the bacterial counts were identical on day 5 for Salmonella-infected mice. Microscopic analysis revealed qualitatively similar inflammatory responses in the spleens and livers of the two types of mice. Specific immunofluorescence staining analyzed by fluorescence-activated cell sorting revealed similar numbers of macrophages and dendritic cells in infected CapG−/− and CapG+/+ spleens. However, analysis of bone marrow-derived macrophages revealed a 50% reduction in the rate of phagocytosis of Listeria in CapG−/− cells but a normal rate of phagocytosis of Salmonella. Stimulation of bone marrow-derived dendritic cells with granulocyte-macrophage colony-stimulating factor resulted in a reduction in the ruffling response of CapG−/− cells compared to the response of CapG+/+ cells, and CapG−/− bone-marrowed derived neutrophils migrated at a mean speed that was nearly 50% lower than the mean speed of CapG+/+ neutrophils. Our findings suggest that specific motility deficits in macrophages, dendritic cells, and neutrophils render CapG−/− mice more susceptible than CapG+/+ mice to Listeria infection.