Genetic background of attenuated Salmonella typhimurium has profound influence on infection and cytokine patterns in human dendritic cells
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Date
2001Author
Dreher, Donatus
Kok, Menno
Cochand, Laurence
Kiama, S G
Gehr, Peter
Peche`, Jean-Claude
Nicod, Laurent Pierre
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
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-alpha 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.
URI
http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/14323http://www.ncbi.nlm.nih.gov/pubmed/11310844
Citation
Journal of Leukocyte Biology Volume 69, April 2001Subject
host defensevaccine vectors
antigen-presenting cells
apoptosis
interleukin-10
interleukin-12