Endosomal and lysosomal nucleic acid

Endosomal and lysosomal nucleic acids refer to DNA and RNA molecules located within the endocytic pathway, where they serve as ligands for Pattern Recognition Receptors (PRRs), specifically Toll-like receptors 3, 7, 8, and 9 (Saas et al., 2023). These nucleic acids can be of exogenous origin, such as viral or bacterial genomes, or endogenous origin, such as self-DNA/RNA released during cell death or through autophagy. The recognition of these molecules is a fundamental component of the innate immune response, triggering the production of type I interferons and other pro-inflammatory cytokines to combat infection. However, the persistent presence or improper sensing of self-nucleic acids in these compartments is a hallmark of autoimmune diseases like systemic lupus erythematosus (SLE) and Sjögren's syndrome. Therapeutic agents like hydroxychloroquine target these nucleic acids by binding to them directly or by neutralizing the acidic environment of the endolysosome, thereby preventing the activation of the TLR signaling cascade and reducing chronic inflammation (Schrezenmeier & Dörner, 2020).

Other names

Endosomal DNAEndosomal RNALysosomal DNALysosomal RNASelf-nucleic acidToll-like receptor ligand

Inhibition of Toll-like receptor (TLR) signaling through direct binding to nucleic acids (masking them from receptors) and elevation of endosomal/lysosomal pH, which prevents the proteolytic activation of TLRs and the processing of their ligands (Schrezenmeier & Dörner, 2020; Kuznik et al., 2011).