Despite being both treatable and curable, tuberculosis, caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the deadliest infectious diseases. Development of new treatments, especially in the face of persistent drug-resistant strains of Mtb, will require a deeper understanding of tuberculosis’s pathophysiology.
Making use of an underutilized approach to small RNA sequencing, termed T4 PNK-seq, Dr. Kirino’s team comprehensively profiled the small non-coding RNAs accumulated in the blood plasma of Mtb patients, and compared these to healthy controls. They found that 5´-derived transfer RNA fragments (tRFs) were especially accumulated in Mtb-patient plasma, along with ribosomal RNA-derived fragments (rRFs). Among the most abundant tRFs were 5´-halves, such as a 5´-half from tRNAHisGUG and 5´-half from tRNAValCAC/AAC, that are known to be potent activators of the pattern recognition receptor Toll-like receptor 7 (TLR7), an activity which associates them with pro-inflammatory immune activation. Moreover, the results suggest that these molecules circulate within extracellular vesicles. The team further identified new molecules, namely rRFs, which were also activators of TLR7. These newly identified TLR7-stimulating rRFs exert an anti-bacterial effect, preventing E. coli infection of cultured human monocyte-derived macrophages. Together, the findings offer insights into a potential small non-coding RNA-driven aspect of host immune response to Mtb infection.
References
- Gumas, J, Kawamura, T, Shigematsu, M, Kirino, Y. Immunostimulatory short non-coding RNAs in the circulation of patients with tuberculosis infection. Mol Ther Nucleic Acids. 2024;35 (1):102156. doi: 10.1016/j.omtn.2024.102156. PubMed PMID:38481936 PubMed Central PMC10933579.
