* Division of Pneumology, University Hospital of Geneva, Switzerland;
Department of Genetics and Microbiology, University of Geneva, Geneva, Switzerland; and
Institute of Anatomy, University of Berne, Berne, Switzerland
Correspondence: Dr. Donatus Dreher, Division of Pneumology, Centre Médical Universitaire, 1, rue Michel-Servet, 1211 Geneva-4, Switzerland. E-mail: dreher{at}dim.hcuge.ch
Salmonella typhimurium (ST) can cause infection in
man, and attenuated strains are under consideration as live vaccine
vectors. However, little is known about the interaction of ST with
human dendritic cells (DC). Here, we compared the consequences of
exposure of human, monocyte-derived DC with different attenuated
strains of ST. Infection was observed with all four strains tested
(wild type, PhoP-, PhoPc, and AroA), but the PhoPc strain
was by far the most efficient. Intracellular persistence of wild type
and PhoP- was longer than that of PhoPc and AroA, both of
which were largely eliminated within 24 h. Most DC survived
infection by the attenuated strains, although apoptosis was observed in
a fraction of the exposed cells. All strains induced DC maturation,
independent from the extent of infection. Although all strains
stimulated secretion of TNF-
and IL-12 strongly, PhoPc induced
significantly less IL-10 than the other three strains and as much as 10
times less IL-10 than heat-killed PhoPc, suggesting that this mutant
suppressed the secretion of IL-10 by the DC. These data indicate that
infectivity, bacterial elimination, and cytokine secretion in human DC
are controlled by the genetic background of ST.
Key Words: host defense • vaccine vectors • antigen-presenting cells • apoptosis • interleukin-10 • interleukin-12
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