Bacterial remnants in chloroplast RNA induce immune responses via mouse TLR13 and human TLR7

According to the endosymbiotic theory, chloroplasts originate from cyanobacteria. While bacteria-derived molecules trigger immune responses via pathogen-associated molecular patterns, the immunological impact of chloroplast-derived molecules remains unclear. Here, we demonstrate that chloroplast RNA induces immune responses in mammalian cells. Using RNA sequencing analysis of total RNA extracted from Arabidopsis thaliana chloroplasts and nuclear factor-kappa B (NF-κB) reporter assays, we identify a 15-base chloroplast RNA sequence that activates NF-κB in mouse cells via Toll-like receptor (TLR)13. Additionally, a 33-base sequence containing this 15-base motif is identified that activates human cells via TLR7. This 15-base sequence is homologous to the bacterial 23S ribosomal RNA ligand for TLR13 but exhibits distinct reactivity. We also detect this 15-base sequence in the chloroplast RNA from radish, spinach, and broccoli. These findings highlight the retention of bacterial features in chloroplasts and suggest that dietary chloroplast RNA may modulate mammalian immune responses, potentially mimicking probiotic effects.