Immunostimulatory short non-coding RNAs in the circulation of patients with tuberculosis infection.
Mol Ther Nucleic Acids
; 35(1): 102156, 2024 Mar 12.
Article
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| MEDLINE
| ID: mdl-38481936
ABSTRACT
Mycobacterium tuberculosis (Mtb) infection is among the world's deadliest infectious diseases. Developing effective treatments and biomarkers for tuberculosis requires a deeper understanding of its pathobiology and host responses. Here, we report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma samples from Mtb-infected patients. We achieved this by pre-treating plasma RNAs with T4 polynucleotide kinase to convert all RNA ends to those compatible with sncRNA sequencing. We discovered a global and drastic upregulation of plasma sncRNAs in Mtb-infected patients, with tRNA-derived sncRNAs representing the most dramatically elevated class. Most of these tRNA-derived sncRNAs originated from a limited subset of tRNAs, specifically from three tRNA isoacceptors, and exhibited skewed patterns to 5'-derived fragments, such as 5' halves, 5' tRNA fragments (tRFs), and internal tRFs (i-tRFs) from the 5' regions. Further, Mtb-infected patients displayed markedly upregulated and distinct profiles of both rRNA- and mRNA-derived sncRNAs. Some of these sncRNAs, which are abundant and specific to Mtb-infected patients, robustly activated human macrophages via Toll-like receptor 7 and induced cytokine production. This drastic accumulation of circulating, immunostimulatory sncRNAs in the plasma of Mtb-infected patients offers insights into the sncRNA-driven aspects of host immune response against infectious diseases and suggests a pool of potential therapeutic targets and biomarkers.
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Bases de datos:
MEDLINE
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En
Revista:
Mol Ther Nucleic Acids
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos