MicroRNA-Mediated Host–Pathogen Communication in Infectious and Parasitic Diseases: From Molecular Mechanisms to Biomarkers and Therapeutic Strategies

Abstract

MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of host–pathogen interactions and provide a complex molecular layer controlling the outcome of infectious and parasitic diseases. This review summarizes current understanding of miRNA-mediated communication across viral, bacterial, fungal, protozoan, and helminth infections, with particular emphasis on bidirectional regulation between host and pathogen. Infection-induced host miRNAs can modulate pathogen replication, immune recognition, inflammation, apoptosis, autophagy, metabolism, and cellular survival, whereas pathogen-derived miRNAs and miRNA-like small RNAs may manipulate host signaling pathways to promote immune evasion, persistence, and disease progression. The review further highlights extracellular vesicles, particularly exosomes, as potential carriers facilitating the transfer of regulatory miRNAs between infected and uninfected cells and potentially across species. These interactions involve major immune and signaling pathways, including Toll-like receptor, NF-κB, interferon, JAK/STAT, and MAPK pathways, demonstrating the broad regulatory capacity of miRNAs during infection. In addition, infection-associated circulating and extracellular-vesicle miRNAs show considerable promise as minimally invasive biomarkers for disease detection, prognosis, disease monitoring, and treatment response. Emerging therapeutic approaches, including miRNA mimics, antagomiRs, and locked-nucleic-acid-based inhibitors, offer opportunities for host-directed intervention. However, clinical translation remains limited by target specificity, off-target effects, delivery efficiency, RNA stability, tissue accessibility, immunogenicity, and insufficient experimental validation, particularly for parasite-derived miRNAs. Integrating small-RNA sequencing, bioinformatics, RT-qPCR, extracellular-vesicle profiling, transcriptomics, proteomics, and functional validation may accelerate the development of reliable miRNA biomarkers and therapeutic strategies for infectious and parasitic diseases.