Gene silencing guided by small regulatory RNAs (sRNAs) governs a broad range of cellular processes in plants. Recently, plant sRNAs were found to serve as mobile silencing agents that confer resistance to eukaryotic pathogens by targeting pathogen transcripts in a trans-species manner. This defense mechanism is termed host-induced gene silencing (HIGS). Despite its promise in broad-spectrum disease resistance, the molecular details of HIGS are poorly understood, constraining its applications in agriculture. Here, I will discuss our recent findings and on-going efforts in understanding the HIGS process using the Arabidopsis thaliana-Phytophthora capsici pathosystem. We show that a specific class of plant sRNAs, secondary small interfering RNAs (siRNA), are important executors of HIGS. An evolutionarily conserved clade of pentatricopeptide repeat (PPR) genes serve as a major source of siRNA production. These PPR genes undergo extensive within-species diversification, which leads to the accumulation of a diverse pool of siRNAs. This is consistent with an engagement of the secondary siRNAs in a co-evolutionary arms race with the pathogens. We also identified an Argonaute protein that plays a key role in pathogen-induced secondary siRNA accumulation. Immune activation leads to increased accumulation of this Argonaute and induces the formation of distinct cytoplasmic condensates that enable siRNA biogenesis. These findings offer new opportunities to enhance disease resistance by implementing siRNA-based defense in the canonical plant immune network.
