Orchestration of the protective immune response to intracellular bacteria: Francisella tularensis as a model organism

Francisella tularensis is used as a model organism in studies of mechanisms behind the induction of a protective T-cell response in the mammalian host. Protective immunity is associated with a CD4 and CD8 T-cell response towards a mosaic of proteins of F. tularensis and due to HLA restriction, each individual selects her own mosaic. No single protein has so far been shown to be immunodominant. Only live F. ru!ni-ei?sis affords effective host protection. Subcellular antigen preparations induce only a marginal protective response even when combined with potent adjuvants such as immunostimulating complexes (ISCOMs). In mice, intradermal injection of live F: tularensis but not of frilled bacteria results in an early cytokine expression in the infected liver, including interleukin-12, tumor necrosis factor-alpha, and interferon-gamma. This cytokine response seems to be a prerequisite for effective priming of T cells to an al-ray of proteins of F. tularensis to occur.