Host DNA Induced Inflammation and Autoimmune Diseases

DNA sensors initiate innate immune responses upon recognition of microbial and self-derived DNA in the intracellular compartments or cytoplasm. These sensors include TLR9, AIM2 like receptors and many other recently identified cytosolic DNA sensors. The otherwise protective nature of host defense by these receptors can turn hostile when they recognize self-DNA through various mechanisms and aberrantly activate DNA sensing pathways leading to unregulated or inappropriate type I IFN production and consequent autoimmune and autoinflammatory diseases. In this chapter, we highlight the current findings that shed light on the complex initiator and effector mechanisms that contribute to autoimmune disease pathology, including DNA sensing receptors, self and non-self discrimination, type I IFN system, mechanisms of enhanced self-DNA access to TLR9 and defective host DNA clearance.