Temporal cytokine profiling of Francisella tularensis-infected human peripheral blood mononuclear cells

BACKGROUND AND PURPOSE: Francisella tularensis is an intracellular bacterium known to replicate in monocytes and macrophages and cause tularemia in humans. Because of its infectious nature, F. tularensis is considered a biowarfare agent. Early cytokine profiles of Francisella-infected human peripheral blood mononuclear cells were evaluated. METHODS: Populations of human peripheral blood mononuclear cells were infected in vitro with F. tularensis live vaccine strain at a very low multiplicity of infection of 1:10 (bacteria:cells). A multiplex bead kit which analyzes 30 cytokines, chemokines and growth factors was utilized to measure secreted cytokines in cell supernatants 1, 4, 8, 16, and 24 h post-infection. RESULTS: Compared with uninfected controls, infected cells showed no increase in cytokine secretion at 1 and 4 h, implying a threshold for activation of immune responses. Starting at 8 h post-infection and continuing through to 24 h, an array of cytokines and growth factors was secreted by the infected cells. Some cytokines not previously associated with Francisella infection in humans were detected at 8 h, including interleukin-17 and interleukin-1 receptor agonist and vascular endothelial growth factor. CONCLUSIONS: The cytokine profiles of F. tularensis-infected peripheral blood mononuclear cells indicate an intricate pattern of both pro- and anti-inflammatory responses, including early T-cell activation.