Involvement of nucleic acid-sensing toll-like receptors in human diseases and their controlling mechanisms

Abstract The innate immune system is the host’s initial response to eliminate pathogens and repair tissue damage. Innate immune cells, such as macrophages and dendritic cells, use pattern recognition receptors (PRRs) to recognize microbial structures and stress-induced molecules released from dead o...

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Bibliographic Details
Main Authors: You-Sheng Lin, Yung-Chi Chang, Tzu-Yu Pu, Tsung-Hsien Chuang, Li-Chung Hsu
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Biomedical Science
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Online Access:https://doi.org/10.1186/s12929-025-01151-9
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Summary:Abstract The innate immune system is the host’s initial response to eliminate pathogens and repair tissue damage. Innate immune cells, such as macrophages and dendritic cells, use pattern recognition receptors (PRRs) to recognize microbial structures and stress-induced molecules released from dead or damaged cells, thereby initiating immune responses. Among PRRs, Toll-like receptors (TLRs) are well-studied and are located either on the cell surface or in endosomal compartments. Most endosomal TLRs specifically recognize nucleic acids and are thus referred to as nucleic acid (NA)-sensing TLRs. Upon activation, these receptors induce the production of inflammatory cytokines and type I interferons and initiate subsequent adaptive immunity. These immune responses work to suppress pathogens and inhibit tumor growth. However, excessive cytokine and interferon production can lead to various inflammatory diseases. This review focuses on mammalian nucleic acid-sensing TLRs, summarizing the molecular regulation of their activations, the impact of their dysregulation on human diseases, and therapeutic strategies that target these TLRs.
ISSN:1423-0127