In this issue of the JCI, Lang et al. (6) demonstrate that LCMV infection precipitates autoimmune hepatitis in a mouse model through activation of TLR3 in antigen-presenting cells, such as macrophages and DCs. Upon activation, cells secrete IFN-α/β and TNF-α, which trigger release of CXCL9 by hepatocytes, Kupffer cells, endothelial cells, and possibly other cells. CXCL9 attracts CXCR3-positive self-reactive CD8⁺ T cells that cause liver damage. As individual viruses can be detected in multiple antigen-presenting cells by different sensors, the figure also illustrates the potential involvement of other antigen-presenting cells, such as plasmacytoid DCs, and other viral sensors, such as TLR7, TLR9, and the RNA helicases melanoma differentiation–associated protein 5 (MDA-5) and retinoic acid–inducible gene I (RIG-I) in triggering autoimmunity. dsRNA, double-stranded RNA; ssRNA, single-stranded RNA.