Cell-Autonomous Immunity: From Cytosolic Sensing to Self-Defense

TL;DR

Non-immune cells can detect and fight intracellular pathogens through cell-autonomous immunity, using specific sensors and signaling pathways.

Contribution

This review provides a comprehensive analysis of cytosolic sensing mechanisms and their roles in disease pathogenesis.

Findings

Cytosolic sensors like cGAS-STING and RIG-I-like receptors detect pathogen-associated molecular patterns.

Cell-autonomous immunity pathways contribute to autoimmune and inflammatory diseases.

These pathways represent potential therapeutic targets for various conditions.

Abstract

As an evolutionarily conserved and ubiquitous mechanism of host defense, non-immune cells in vertebrates possess the intrinsic ability to autonomously detect and combat intracellular pathogens. This process, termed cell-autonomous immunity, is distinct from classical innate immunity. In this review, we comprehensively examine the defense mechanisms employed by non-immune cells in response to intracellular pathogen invasion. We provide a detailed analysis of the cytosolic sensors that recognize aberrant nucleic acids, lipopolysaccharide (LPS), and other pathogen-associated molecular patterns (PAMPs). Specifically, we elucidate the molecular mechanisms underlying key signaling pathways, including the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs)-mitochondrial antiviral signaling (MAVS) axis, and the guanylate-binding proteins (GBPs)-mediated pathway. Furthermore, we critically evaluate the involvement of these pathways in the pathogenesis of various diseases, including autoimmune disorders, inflammatory conditions, and malignancies, while highlighting their potential as therapeutic targets.

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