Toll-like receptors 3, 7, and 9 respond to foreign or, as shown in the cross-section of a dendritic cell, host-derived nucleic acids. Following Unc93b1-mediated transport from the endoplasmic reticulum to endolysosomes, these TLRs are activated by ligation of DNA and RNA. This engagement triggers downstream signaling events that ultimately lead to activation of B cells to produce antibodies that attack the host's own tissues and organs, a hallmark of lupus. Illustration by Mary O'Reilly.