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Infection and Immunity, March 2001, p. 1344-1350, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1344-1350.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Listeria monocytogenes-Infected Phagocytes Can Initiate Central Nervous System Infection in Mice

Douglas A. Drevets,1,* Todd A. Jelinek,1 and Nancy E. Freitag2

Department of Medicine, Oklahoma University Health Sciences Center and the Harold Muchmore Laboratories for Infectious Diseases Research of the Veterans Administration Medical Center, Oklahoma City, Oklahoma,1 and The Seattle Biomedical Research Institute, Seattle, Washington2

Received 8 August 2000/Returned for modification 15 September 2000/Accepted 17 November 2000

Listeria monocytogenes-infected phagocytes are present in the bloodstream of experimentally infected mice, but whether they play a role in central nervous system (CNS) invasion is unclear. To test whether bacteria within infected leukocytes could establish CNS infection, experimentally infected mice were treated with gentamicin delivered by surgically implanted osmotic pumps. Bacterial inhibitory titers in serum and plasma ranged from 1:16 to 1:256, and essentially all viable bacteria in the bloodstream of treated mice were leukocyte associated. Nevertheless, CNS infection developed in gentamicin-treated animals infected intraperitoneally or by gastric lavage, suggesting that intracellular bacteria could be responsible for neuroinvasion. This was supported by data showing that 43.5% of bacteria found with blood leukocytes were intracellular and some colocalized with F-actin, indicating productive intracellular parasitism. Experiments using an L. monocytogenes strain containing a chromosomal actA-gfpuv-plcB transcriptional fusion showed that blood leukocytes were associated with intracellular and extracellularly bound green fluorescent protein-expressing (GFP+) bacteria. Treatment with gentamicin decreased the numbers of extracellularly bound GFP+ bacteria significantly but did not affect the numbers of intracellular GFP+ bacteria, suggesting that the latter were the result of intercellular spread of GFP+ bacteria to leukocytes. These data demonstrate that infected leukocytes and the intracellular L. monocytogenes harbored within them play key roles in neuroinvasion. Moreover, they suggest that phagocytes recruited to infected organs such as the liver or spleen are themselves parasitized by intercellular spread of L. monocytogenes and then reenter the bloodstream and contribute to the systemic dissemination of bacteria.

* Corresponding author. Mailing address: Section of Infectious Diseases, University of Oklahoma Health Sciences Center, VA Medical Center (111/c), Oklahoma City, OK 73104. Phone: (405) 270-0501, ext. 3284. Fax: (405) 297-5934. E-mail: douglas-drevets{at}ouhsc.edu.

Infection and Immunity, March 2001, p. 1344-1350, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1344-1350.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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