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Review

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

1
The First Clinical Medical College, Zhengzhou University, Zhengzhou 450052, China
2
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(9), 4025; https://doi.org/10.3390/ijms26094025
Submission received: 15 March 2025 / Revised: 16 April 2025 / Accepted: 22 April 2025 / Published: 24 April 2025
(This article belongs to the Section Molecular Immunology)

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.
Keywords: cell-autonomous immunity; 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; guanylate-binding proteins (GBPs); intracellular pathogens cell-autonomous immunity; 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; guanylate-binding proteins (GBPs); intracellular pathogens

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MDPI and ACS Style

Han, D.; Zhang, B.; Wang, Z.; Mi, Y. Cell-Autonomous Immunity: From Cytosolic Sensing to Self-Defense. Int. J. Mol. Sci. 2025, 26, 4025. https://doi.org/10.3390/ijms26094025

AMA Style

Han D, Zhang B, Wang Z, Mi Y. Cell-Autonomous Immunity: From Cytosolic Sensing to Self-Defense. International Journal of Molecular Sciences. 2025; 26(9):4025. https://doi.org/10.3390/ijms26094025

Chicago/Turabian Style

Han, Danlin, Bozheng Zhang, Zhe Wang, and Yang Mi. 2025. "Cell-Autonomous Immunity: From Cytosolic Sensing to Self-Defense" International Journal of Molecular Sciences 26, no. 9: 4025. https://doi.org/10.3390/ijms26094025

APA Style

Han, D., Zhang, B., Wang, Z., & Mi, Y. (2025). Cell-Autonomous Immunity: From Cytosolic Sensing to Self-Defense. International Journal of Molecular Sciences, 26(9), 4025. https://doi.org/10.3390/ijms26094025

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