Neutrophil sensing of cytoplasmic, pathogenic DNA in a cGAS-STING-independent manner.

Abstract

The innate immune system is an integral part of the host response to invading pathogens and endogenous danger signals. Pattern recognition receptors (PRRs), which are utilized by the innate immune system, can detect pathogen-associated molecular patterns (PAMPs) of invading pathogens and damage-associated molecular patterns (DAMPs) and signal to initiate the innate immune response.1,2 Upon recognition by PRRs, the receptor activates downstream signaling pathways, leading to the production of proinflammatory cytokines and type I interferons (IFNs), which function to eliminate the invading pathogens or, alternatively, cause inflammatory and autoimmune diseases.1,2 Nucleic acids, which exist in all living organisms, are important danger signals when detected by the innate immune system in certain unfamiliar locations or chemical states. PRRs have been implicated in the detection of RNA and DNA derived from both pathogens and hosts; examples include Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), AIM2-like receptors (ALRs), and NOD-like receptors (NLRs).1,2 Understanding the mechanisms that govern immune cell recognition of pathogenic DNA is crucial for elucidating the anti-microbial and autoimmune responses.