Connections between antiviral defense and autoimmunity

Abstract

Recent advances have revealed a fundamental contradiction in antiviral immunity: innate immune sensors that detect nucleic acids mediate both protective immunity to infection and pathological autoimmune disease. Thus, the study of the mechanics of nucleic acid detection will provide insight into how these systems are inappropriately triggered in autoimmunity, and, conversely, the study of autoimmune disease triggered by these sensors will tell us more about how they are linked to activation of adaptive immunity.

Figure 1. A continuum model of autoimmunity

At least three mechanisms can drive activation of lymphocyte-dependent autoimmune pathology, each with unique requirements for regulation and distinct connections to adaptive immunity. Examples of each mechanism and the points at which they affect autoimmunity are shown in the highlighted boxes: (a) defective lymphocyte tolerance (blue boxes); (b) dysregulated TLR detection (green boxes); and (c) cell-intrinsic initiation by cytosolic nucleic acid sensors (red boxes). Please see the text for details.