Identification of Aim2 as a sensor for DNA vaccines
Department of Medicine, Division of Infectious Diseases and Immunology, Program in Innate Immunity; Department of Medicine, Laboratory of Nucleic Acid Vaccines
Animals; DNA-Binding Proteins; Humans; Immunity, Innate; Inflammasomes; Interferon-alpha; Interferon-beta; Interleukin-18; Interleukin-1beta; Mice; Mice, Knockout; *Vaccines, DNA
Recent human study data have re-established the value of DNA vaccines, especially in priming high-level Ag-specific Ab responses, but also raised questions about the mechanisms responsible for such effects. Whereas previous reports have shown involvement of downstream signaling molecules in the innate immune system, the current study investigated the role of absent in melanoma 2 (Aim2) as a sensor for DNA vaccines. The Aim2 inflammasome directs maturation of the proinflammatory cytokines IL-1beta and IL-18 and an inflammatory form of cell death called pyroptosis. Both the humoral and cellular Ag-specific adaptive responses were significantly reduced in Aim2-deficient mice in an IL-1beta/IL-18-independent manner after DNA vaccination. Surprisingly, Aim2-deficient mice also exhibited significantly lower levels of IFN-alpha/beta at the site of injection. These results indicate a previously unreported link between DNA vaccine-induced pyroptotic cell death and vaccine immunogenicity that is instrumental in shaping the Ag-specific immune response to DNA vaccines.
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Citation: J Immunol. 2015 Jan 15;194(2):630-6. doi: 10.4049/jimmunol.1402530. Link to article on publisher's site
Suschak, John; Wang, Shixia; Fitzgerald, Katherine A.; and Lu, Shan, "Identification of Aim2 as a sensor for DNA vaccines" (2015). Infectious Diseases and Immunology Publications and Presentations. 195.