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

Salmonella typhimurium (ST) can cause infection in man, and attenuated stra ins are under consideration as live vaccine vectors. However, little is kno wn shout the interaction of ST with human dendritic cells (DC), Here, we co mpared the consequences of exposure of human, monocyte-derived DC with diff erent attenuated strains of ST. Infection was observed with ah 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- wa s longer than that of PhoPc and AroA, both of which were largely eliminated within 24 h, Most DC survived infection by the attenuated strains, althoug h apoptosis was observed in a fraction of the exposed cells. Ail strains in duced DC maturation, independent from the extent of infection. Although all strains stimulated secretion of TNF-alpha and IL-12 strongly, PhoPc induce d significantly less IL-10 than the other three strains auld as much as 10 times less IL-10 than heat-killed PhoPc, suggesting that this mutant suppre ssed 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.