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

• DOI: 10.1128/iai.71.11.6582-6590.2003
• Publication Date: 2003-10-24T02:31:56Z
• Authors: Shefal S. Parikh; Sally A. Litherland; Michael J. Clare-...; Wei Li; Paul A. Gulig; Frederick S. Sout...
• Keywords: Salmonella typhimurium; 0301 basic medicine; Mice, Inbred BALB C; Salmonella Infections, Animal; Neutrophils; Macrophages; Microfilament Proteins; Nuclear Proteins; Flow Cytometry; 3. Good health; Lethal Dose 50; Mice, Inbred C57BL; Chemotaxis, Leukocyte; Mice; 03 medical and health sciences; Liver; Phagocytosis; Animals; Listeriosis; Disease Susceptibility; Spleen

ABSTRACT

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 × 10 3 CFU for CapG −/− mice and 6 × 10 4 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.