Toll-free autoimmunity

Self-DNA and pathogen-derived DNA take different routes to immune activation, say Okabe and colleagues (page 1333). Thus, it may be possible to block an autoimmune response to self-DNA without compromising the beneficial response to pathogenic DNA.

Microbial DNA is mopped up by macrophages and dendritic cells, which get activated via Toll-like receptors (TLRs), resulting in the production of interferon-β (IFNβ). Recent studies have shown that mammalian DNA complexed to antibodies can also trigger IFNα production via a TLR (specifically TLR9).

The immune system can also be activated by naked self-DNA, leading to some autoimmune diseases. One such state occurs in mice lacking DNaseII. These mice accumulate undigested self-DNA from dead cells in their macrophages, and act as a model for systemic lupus erythematosus (SLE), a disease characterized by autoantibodies to circulating self-DNA.

The up-regulation...