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Infection and Immunity, October 2000, p. 5702-5709, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Salmonella Pathogenicity Island
1-Independent Induction of Apoptosis in Infected Macrophages by
Salmonella enterica Serotype Typhimurium
Adrianus W. M.
van der
Velden,1
Susanne W.
Lindgren,1,2
Micah J.
Worley,1 and
Fred
Heffron1,*
Department of Molecular Microbiology and Immunology, Oregon
Health Sciences University, Portland, Oregon
97201-3098,1 and Department of Biology,
California State University, Sacramento, California
95819-60772
Received 14 April 2000/Accepted 30 June 2000
The enteric pathogen Salmonella enterica serotype
Typhimurium induces apoptosis in infected macrophages. This process is
rapid, specific, and depends on the type III protein secretion system encoded within Salmonella pathogenicity island 1 (SPI1).
Here, we demonstrate that serotype Typhimurium can activate programmed macrophage cell death independently of SPI1. SPI1 independent induction
of apoptosis in infected macrophages is observed as early as 12 to
13 h postinfection, even in the absence of intracellular bacterial
replication. Delayed activation of programmed macrophage cell death is
not observed with serotype Typhimurium strains mutated in
ompR or SPI2. Even though SPI2 mutants have a defect in
intracellular proliferation, our results indicate that long-term
intracellular survival and growth are not required for delayed
macrophage killing per se, since Salmonella mutants that
are severely defective in intracellular growth still induce delayed
apoptosis. Inactivation of genes required for either rapid or delayed
induction of apoptosis results in a conditional noncytotoxic phenotype,
whereas simultaneous inactivation of genes required for both rapid and
delayed induction of apoptosis renders serotype Typhimurium
noncytotoxic under all conditions tested. Our hypothesis is that
differential activation of programmed macrophage cell death by serotype
Typhimurium occurs under discrete physiological conditions at distinct
locations within an infected host.
*
Corresponding author. Mailing address: Department of
Molecular Microbiology and Immunology, Oregon Health Sciences
University, 3181 SW Sam Jackson Park Rd., L220, Portland, OR
97201-3098. Phone: (503) 494-6738. Fax: (503) 494-6862. E-mail:
heffronf{at}ohsu.edu.
Infection and Immunity, October 2000, p. 5702-5709, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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