Bacillus anthracis, the causative agent of anthrax, can cause immunosuppression with uncontrolled bacteraemia, multisystem dysfunction, and, ultimately, death. The critical virulence factor of B. anthracis is lethal toxin (LT), which affects many cell types, including macrophages. The interaction between B. anthracis components and dendritic cells results in the activation of immune suppression mechanisms, but the precise nature of these systems has been unclear. In the July 17 Nature, Anshu Agrawal and colleagues at the Emory Vaccine Research Center show that LT impairs the function of dendritic cells and host immune responses by disrupting MAP kinase signaling (Nature, 424:329-334, July 17, 2003).

Agrawal et al. used mouse splenic dendritic cells exposed to LT in vitro and in vivo. They observed that when stimulated with lipopolysaccharide, dendritic cells did not upregulate costimulatory molecules, secreted greatly diminished amounts of proinflammatory cytokines, and did not effectively stimulate antigen-specific T...

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