Building better vaccines: how apoptotic cell death can induce inflammation and activate innate and adaptive immunity.

The immunological consequences of apoptosis have been hotly debated. Apoptosis was originally described as a set of cellular morphological changes that occur in the absence of inflammation but the term has been redefined on the basis of a set of conserved molecular events that include the activation of caspases. Though the apoptosis occurring during normal development is immunologically bland or even tolerizing, the apoptotic death after viral infection or after the ligation of Fas can trigger powerful innate and adaptive immune responses. The molecular machinery at the nexus of apoptosis and inflammation includes caspase-1 --an activator of IL-1beta and IL-18 - as well as the double-stranded-RNA-dependent protein kinase pathway and RNaseL pathway, which are key effectors of antiviral immunity. New proapoptotic vaccines induce immune responses that may be able to prevent or treat infectious disease and cancer.