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Genetic background of attenuated Salmonella typhimurium has profound influence on infection and cytokine patterns in human dendritic cells
Author(s) -
Dreher Donatus,
Kok Menno,
Cochand Laurence,
Gitahi Kiama Stephen,
Gehr Peter,
Pechère JeanClaude,
Nicod Laurent Pierre
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.69.4.583
Subject(s) - biology , aroa , infectivity , attenuated vaccine , salmonella , microbiology and biotechnology , secretion , congenic , mutant , cytokine , virology , intracellular parasite , intracellular , immune system , enterobacteriaceae , immunology , gene , bacteria , virulence , genetics , virus , escherichia coli , biochemistry
Salmonella typhimurium (ST) can cause infection inman, and attenuated strains are under consideration as live vaccinevectors. However, little is known about the interaction of ST withhuman dendritic cells (DC). Here, we compared the consequences ofexposure of human, monocyte‐derived DC with different attenuatedstrains of ST. Infection was observed with all four strains tested(wild type, PhoP − , PhoPc, and AroA), but the PhoPc strainwas by far the most efficient. Intracellular persistence of wild typeand PhoP − was longer than that of PhoPc and AroA, both ofwhich were largely eliminated within 24 h. Most DC survivedinfection by the attenuated strains, although apoptosis was observed ina fraction of the exposed cells. All strains induced DC maturation,independent from the extent of infection. Although all strainsstimulated secretion of TNF‐α and IL‐12 strongly, PhoPc inducedsignificantly less IL‐10 than the other three strains and as much as 10times less IL‐10 than heat‐killed PhoPc, suggesting that this mutantsuppressed the secretion of IL‐10 by the DC. These data indicate thatinfectivity, bacterial elimination, and cytokine secretion in human DCare controlled by the genetic background of ST.