title: Host DNA released in response to aluminum adjuvant enhances MHC class II-mediated antigen presentation and prolongs CD4 T-cell interactions with dendritic cells.
abstract: Many vaccines include aluminum salts (alum) as adjuvants despite little knowledge of alum's functions. Host DNA rapidly coats injected alum. Here, we further investigated the mechanism of alum and DNA's adjuvant function. Our data show that DNase coinjection reduces CD4 T-cell priming by i.m. injected antigen + alum. This effect is partially replicated in mice lacking stimulator of IFN genes, a mediator of cellular responses to cytoplasmic DNA. Others have shown that DNase treatment impairs dendritic cell (DC) migration from the peritoneal cavity to the draining lymph node in mice immunized i.p. with alum. However, our data show that DNase does not affect accumulation of, or expression of costimulatory proteins on, antigen-loaded DCs in lymph nodes draining injected muscles, the site by which most human vaccines are administered. DNase does inhibit prolonged T-cell-DC conjugate formation and antigen presentation between antigen-positive DCs and antigen-specific CD4 T cells following i.m. injection. Thus, from the muscle, an immunization site that does not require host DNA to promote migration of inflammatory DCs, alum acts as an adjuvant by introducing host DNA into the cytoplasm of antigen-bearing DCs, where it engages receptors that promote MHC class II presentation and better DC-T-cell interactions.
authors: Clinical Immunology Division, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
authors: Amy S
authors: AS
authors: McKee
authors: Matthew A
authors: MA
authors: Burchill
authors: Michael W
authors: MW
authors: Munks
authors: Lei
authors: L
authors: Jin
authors: John W
authors: JW
authors: Kappler
authors: Rachel S
authors: RS
authors: Friedman
authors: Jordan
authors: J
authors: Jacobelli
authors: Philippa
authors: P
authors: Marrack
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004247:DNA / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000941:Antigens; D000949:Histocompatibility Antigens Class II; C041524:aluminum sulfate; D004247:DNA