Salmonella typhi flagella are potent inducers of proinflammatory cytokine secretion by human monocytes

The cytokine production patterns of human peripheral blood mononuclear cell s (PBMC) in response to Salmonella typhi flagella (STF) were examined in cu lture supernatants of PBMC stimulated with STF. Consistent with previous fi ndings in volunteers vaccinated with aroC aroD deletion mutants of S. typhi , PBMC from volunteers immunized with the licensed live Ty21a S. typhi vacc ine secreted gamma interferon following exposure to STP. Stimulation with S TF induced rapid de novo synthesis of tumor necrosis factor alpha (TNF-alph a) and interleukin-1 beta (IL-1 beta), followed by IL-6 and IL-10. Trypsin treatment of STF abrogated their effects, while polymyxin B had no effect. Intracellular cytokine measurements of STF-stimulated PBMC revealed the exi stence of monocyte subpopulations that produce only TNF-alpha, IL-1 beta or both cytokines. Moreover, STF markedly decreased the percentage of CD14(+) cells. These data demonstrate that STF are powerful monocyte activators wh ich may have important implications for vaccine development and for underst anding the pathogenesis of S. typhi infection.