Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minato-ku, Japan.
Faculty of Pharmacy, Department of Pharmaceutical Sciences and Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
Front Immunol. 2022 Jun 23;13:941931. doi: 10.3389/fimmu.2022.941931. eCollection 2022.
Toll-like receptors (TLRs) respond to pathogen constituents, such as microbial lipids and nucleic acids (NAs). TLRs recognize NAs in endosomal compartments. Structural and functional studies have shown that recognition of NAs by TLRs depends on NA processing by RNases and DNases. DNase II-dependent DNA degradation is required for TLR9 responses to single-stranded DNAs, whereas RNase T2-dependent RNA degradation enables TLR7 and TLR8 to respond to nucleosides and oligoribonucleotides. In contrast, RNases and DNases negatively regulate TLR responses by degrading their ligands. RNase T2 negatively regulates TLR3 responses to degrading the TLR3 ligand double-stranded RNAs. Therefore, NA metabolism in the endosomal compartments affects the endosomal TLR responses. Dysregulation of NA metabolism in the endosomal compartment drives the TLR-dependent pathologies in human diseases.
Toll 样受体（TLRs）可识别病原体成分，如微生物脂质和核酸（NAs）。TLRs 在内涵体腔内识别 NAs。结构和功能研究表明，TLRs 对 NAs 的识别取决于 RNase 和 DNase 对 NAs 的加工。TLR9 对单链 DNA 的反应需要依赖于 DNA 酶 II 的 DNA 降解，而依赖于 RNA 酶 T2 的 RNA 降解使 TLR7 和 TLR8 能够对核苷和寡核糖核苷酸作出反应。相比之下，RNase 和 DNase 通过降解其配体来负调控 TLR 反应。RNA 酶 T2 负调控 TLR3 对 TLR3 配体双链 RNA 的反应。因此，内涵体腔内的 NA 代谢会影响内涵体 TLR 反应。内涵体腔内的 NA 代谢失调会导致人类疾病中 TLR 依赖的病理。
