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Infection and Immunity, November 2003, p. 6582-6590, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6582-6590.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Shefal S. Parikh,^1,2 Sally A. Litherland,³ Michael J. Clare-Salzler,^1,3 Wei Li,¹ Paul A. Gulig,² and Frederick S. Southwick^1,2*

Department of Medicine,¹ Department of Molecular Genetics and Microbiology,² Department of Pathology, University of Florida College of Medicine, Gainesville, Florida 32610³

Received 26 December 2002/ Returned for modification 6 February 2003/ Accepted 28 July 2003

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 x 10³ CFU for CapG^-/- mice and 6 x 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.

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* Corresponding author. Mailing address: Division of Infectious Diseases, Department of Medicine, P.O. Box 100277, Health Science Center, Gainesville, FL 32610-0277. Phone: (352) 392-2928. Fax: (352) 392-6481. E-mail: southfs{at}medmac.ufl.edu.

Editor: F. C. Fang

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Infection and Immunity, November 2003, p. 6582-6590, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6582-6590.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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