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Infection and Immunity, March 2000, p. 1005-1013, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Differential Bacterial Survival, Replication, and
Apoptosis-Inducing Ability of Salmonella Serovars within
Human and Murine Macrophages
William R.
Schwan,1,2
Xiao-Zhe
Huang,1
Lan
Hu,1 and
Dennis J.
Kopecko1,*
Laboratory of Enteric and Sexually
Transmitted Diseases, Center for Biologics Evaluation and Research,
Food and Drug Administration, Bethesda, Maryland
20892,1 and Department of Biology
and Microbiology, University of Wisconsin
La Crosse, La Crosse,
Wisconsin 546012
Received 12 March 1999/Returned for modification 4 May
1999/Accepted 12 November 1999
Salmonella serovars are associated with human diseases
that range from mild gastroenteritis to host-disseminated enteric
fever. Human infections by Salmonella enterica serovar
Typhi can lead to typhoid fever, but this serovar does not typically
cause disease in mice or other animals. In contrast, S. enterica serovar Typhimurium and S. enterica
serovar Enteritidis, which are usually linked to localized
gastroenteritis in humans and some animal species, elicit a systemic
infection in mice. To better understand these observations, multiple
strains of each of several chosen serovars of Salmonella
were tested for the ability in the nonopsonized state to enter,
survive, and replicate within human macrophage cells (U937 and
elutriated primary cells) compared with murine macrophage cells
(J774A.1 and primary peritoneal cells); in addition, death of the
infected macrophages was monitored. The serovar Typhimurium strains all demonstrated enhanced survival within J774A.1 cells and
murine peritoneal macrophages, compared with the significant, almost
100-fold declines in viable counts noted for serovar Typhi strains.
Viable counts for serovar Enteritidis either matched the level of
serovar Typhi (J774A.1 macrophages) or were comparable to counts for
serovar Typhimurium (murine peritoneal macrophages). Apoptosis was significantly higher in J774A.1 cells infected with serovar Typhimurium strain LT2 compared to serovar Typhi strain Ty2. On
the other hand, serovar Typhi survived at a level up to 100-fold
higher in elutriated human macrophages and 2- to 3-fold higher in
U937 cells compared to the serovar Typhimurium and
Enteritidis strains tested. Despite the differential multiplication of
serovar Typhi during infection of U937 cells, serovar Typhi caused
significantly less apoptosis than infections with serovar
Typhimurium. These observations indicate variability in intramacrophage
survival and host cytotoxicity among the various serovars and are the
first to show differences in the apoptotic response of distinct
Salmonella serovars residing in human macrophage cells.
These studies suggest that nonopsonized serovar Typhimurium enters,
multiplies within, and causes considerable, acute death of macrophages,
leading to a highly virulent infection in mice (resulting in
death within 14 days). In striking contrast, nonopsonized serovar Typhi
survives silently and chronically within human macrophages,
causing little cell death, which allows for intrahost dissemination
and typhoid fever (low host mortality). The type of disease
associated with any particular serovar of Salmonella
is linked to the ability of that serovar both to persist within
and to elicit damage in a specific host's macrophage cells.
*
Corresponding author. Mailing address: Laboratory of
Enteric and Sexually Transmitted Diseases, HFM440, Food and Drug
Administration, Center for Biologics Evaluation and Research, NIH
Campus, Bldg. 29/420, Bethesda, MD 20892. Phone: (301) 496-1893. Fax:
(301) 480-5047. E-mail: kopecko{at}cber.fda.gov.
Infection and Immunity, March 2000, p. 1005-1013, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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