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Cell-Mediated DNA Transport Between Distant Inflammatory Sites Following Intradermal DNA Immunization in the Presence of Adjuvant¹

Antonio La Cava^2,*, Rosario Billetta^*,¶, Guido Gaietta, Dustan B. Bonnin^*, Stephen M. Baird and Salvatore Albani^§,||

Departments of ^* Medicine, Neuroscience, Pathology, and ^§ Pediatrics, University of California at San Diego, La Jolla, CA 92093; ^¶ Instituto de Ciencias Biomedicas, Immunology Program, School of Medicine, University of Chile, Santiago, Chile; and ^|| Androclus Therapeutics, Catania, Italy

After intradermal genetic immunization, naked DNA is transported from the site of injection to regional lymph nodes. Little is known on how inflammation influences this process and whether DNA is transported beyond local lymph nodes. In the experiments herein reported, we injected naked DNA in the presence of adjuvant to address questions related to 1) the fate of naked DNA in the presence of inflammation; 2) the generation of immune responses to the encoded protein during inflammation; and, more in general, 3) the fate of ingested molecules beyond regional lymph nodes during inflammation. Two sites of inflammation were induced in vivo in mice. Naked DNA was injected in the nape together with adjuvant, and adjuvant only was injected at a distant peritoneal site. Injected DNA, uptaken at the primary dermal site of inflammation, was transported beyond regional lymph nodes to distant organs such as the spleen and to the distant peritoneal site of inflammation. This transport, mediated by CD11b⁺ cells, was cumulative during chronic inflammation. These results indicate a novel route of transport of DNA beyond regional lymph nodes and may have specific implications for DNA-based immune modulation.

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