Genetic background of attenuated Salmonella typhimurium has profound influence on infection and cytokine patterns in human dendritic cells

Abstract

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.