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Infection and Immunity, July 1999, p. 3512-3517, Vol. 67, No. 7
Departments of Medicine and Microbiology and
Immunology, R. C. Byrd Health Sciences Center of West Virginia
University, Morgantown, West Virginia 26506-9163
Received 11 March 1999/Accepted 20 April 1999
In vitro data suggest that blood-borne Listeria
monocytogenes organisms enter the central nervous system (CNS) by
direct invasion of endothelial cells or by cell-to-cell spread from
infected phagocytes to endothelial cells. However, a role for infected
phagocytes in neuroinvasion and dissemination of L. monocytogenes in vivo has not been confirmed experimentally.
Experiments described here tested whether L. monocytogenes-infected peripheral blood leukocytes (PBL)
circulated in bacteremic mice and could establish organ infection in
vivo. A mean of 30.5% of bacteria cultured from whole blood were PBL
associated, and microscopy showed that 22.2% of monocytes and 1.6% of
neutrophils were infected. PBL-associated bacteria spread to
endothelial cells in vitro, indicating their potential for virulence in
vivo. To test this possibility, mice were injected intravenously with
infected PBL and CFU of bacteria in liver, spleen, and brain were
quantified and compared with values for mice injected with broth-grown
bacteria and in vitro-infected macrophage cell lines. An inoculum of
infected macrophage cell lines led to greater numbers of bacteria in
the liver than the numbers produced by a similar inoculum of
broth-grown bacteria. In contrast, brain infection was best established
by infected PBL. Results of intraperitoneal injection of infected
peritoneal cells compared with results of injection with infected
J774A.1 cells suggested that unrestricted intracellular bacterial
replication within J774A.1 cells contributed to excessive liver
infection in those mice. These data show dissemination of intracellular L. monocytogenes and indicate that phagocyte-facilitated
invasion has a role in CNS infection in vivo. Heterogeneity with regard to bactericidal activity as well as to other phagocyte characteristics is a critical feature of this mechanism.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Dissemination of Listeria monocytogenes
by Infected Phagocytes
*
Present 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. 3691. Fax: (405) 297-5934. E-mail: douglas-drevets{at}ouhsc.edu.
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