Hidden Messengers: The Uncharted Role of Microbial Small RNAs in Reprogramming Host Immunity During Chronic Infections

Small RNAs (sRNAs) have emerged as versatile regulators of gene expression in both prokaryotes and eukaryotes. Beyond their intracellular roles, an increasing body of evidence suggests that microbial pathogens release sRNAs that can be sensed, internalized, or even hijacked by host cells. This cross-kingdom communication reprograms immune pathways, shaping the delicate balance between pathogen persistence and host defense. In chronic infections—such as tuberculosis, hepatitis, and persistent fungal or parasitic diseases—microbial sRNAs act as hidden messengers, modulating cytokine networks, evading immune surveillance, and rewiring host epigenetic landscapes.