The role of innate immunity in the induction of autoimmunity.
The autoimmune diseases are a diverse group of conditions characterized by abnormal B and T cell reactivity in association with autoantibody production. Among these diseases, systemic lupus erythematosus (SLE) is notable for the expression of antibodies to DNA, with these antibodies representing diagnostic markers. While mammalian DNA is immunologically inert, DNA from bacteria can potently stimulate the innate immune system, activating both toll-like receptors (TLRs) as well as non-TLR internal receptors. Since the sera of normal humans contain antibodies specific for bacterial DNA, this molecule appears to be immunogenic during infection. In pre-autoimmune mice, immunization with bacterial DNA can induce anti-DNA autoantibody production, suggesting a role in initiating this response. The immune properties of DNA are mutable, however, since mammalian DNA can acquire immunological activity when bound to certain proteins or anti-DNA antibodies to form immune complexes. In SLE, these immune complexes can drive the production of interferon by plasmacytoid dendritic cells, thereby intensifying autoimmunity. Together, these observations suggest that DNA can induce innate as well as adaptive immune responses and promote the pathogenesis of SLE because of its intrinsic immunostimulatory activity.
Pisetsky
David S
DS
Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC, USA. dpiset@mc.duke.edu
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000936:Antigen-Antibody Complex / Q000096:biosynthesis / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D015415:Biomarkers / Q000378:metabolism; D004269:DNA, Bacterial / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D051193:Toll-Like Receptors / Q000378:metabolism*
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D001324:Autoantigens; D015415:Biomarkers; D004269:DNA, Bacterial; D051193:Toll-Like Receptors; D007372:Interferons