UMass Chan Affiliations
Department of Medicine, Laboratory of Nucleic Acid VaccinesDepartment of Medicine, Division of Infectious Diseases and Immunology, Program in Innate Immunity
Document Type
Journal ArticlePublication Date
2015-01-15Keywords
AnimalsDNA-Binding Proteins
Humans
Immunity, Innate
Inflammasomes
Interferon-alpha
Interferon-beta
Interleukin-18
Interleukin-1beta
Mice
Mice, Knockout
*Vaccines, DNA
Immunity
Immunology and Infectious Disease
Immunology of Infectious Disease
Immunoprophylaxis and Therapy
Metadata
Show full item recordAbstract
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.Source
J Immunol. 2015 Jan 15;194(2):630-6. doi: 10.4049/jimmunol.1402530. Link to article on publisher's siteDOI
10.4049/jimmunol.1402530Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34975PubMed ID
25488991Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.1402530