Book Description

Invading microbes are detected by cellular sensors, the consequences of which result in the production of potent anti-pathogen proteins such as type I interferon (IFN) as well as other cytokines capable of stimulating the adaptive immune response. Examples comprise the RIG-I-like helicase (RLH) and the Toll-like receptor (TLR) families which recognize non-self-pathogen derived molecules (PAMPs) including bacterial lipopolysaccharides as well as nucleic acids. In addition, an endoplasmic reticulum (ER) associated transmembrane protein referred to as STING (for stimulator of interferon genes) was established as being essential for triggering the production of innate immune proteins in response to the sensing of cytosolic DNA. Such DNA can be ‘self’-DNA produced from necrotic or apoptotic cells, or the actual genomes of DNA pathogens that become exposed following infection. Moreover, while STING appears essential for controlling innate signaling events triggered by DNA microbes, chronic STING activation also appears to be responsible for certain inflammatory diseases manifested by ‘self’-DNA. Thus, understanding STING function may lead to the design of new compounds that may facilitate vaccine development or conversely that may provide new therapies for the treatment of inflammatory disease.