Salmonella enterica serovar Typhimurium expressing mutant lipid A with decreased endotoxicity causes maturation of murine dendritic cells.
A major Salmonella component involved in cellular activation is the lipopolysaccharide (LPS) molecule which can act as a dendritic cell (DC) stimulator. The structure of the lipid A domain of the LPS molecule dictates its immunostimulatory capacity with various cell types. In this study, the role of lipid A as an integral component of Salmonella in stimulating murine DCs was studied by using a Salmonella enterica serovar Typhimurium lpxM mutant with defective lipid A. This study revealed that a mutation in lpxM did not significantly affect the ability of bacteria to activate DCs. Although the lpxM mutant less tumor necrosis factor alpha, interleukin-1beta, and inducible nitric oxide synthase than the parental strain, this was only seen at lower multiplicities of infection (MOIs). Both strains upregulated surface molecule expression on DCs and augmented the T-cell-stimulating capacity of these cells in an MOI-independent manner. Thus, the lpxM mutation did not appear to affect the stimulatory capacity of the Salmonella mutant.
Kalupahana
Ruwani
R
Centre for Veterinary Science, Department of Clinical Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES, United Kingdom.
Emilianus
A Romina
AR
Maskell
Duncan
D
Blacklaws
Barbara
B
D000818:Animals; D003713:Dendritic Cells / Q000502:physiology*; D007375:Interleukin-1 / Q000096:biosynthesis; D008050:Lipid A / Q000235:genetics* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D008050:Lipid A; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse