Oral RNAi delivery for targeting Ftz-F1β/JAK-STAT signaling axis to boost shrimp immunity against pathogen infection

The JAK-STAT signaling pathway is crucial for antiviral and antibacterial immune responses, as it regulates the expression of a set of immune-related genes in response to pathogen infection. Suppressor of cytokine signaling 2 (SOCS2), a key negative regulator of JAK-STAT signaling, modulates the immune response to prevent excessive activation. The current study identified a fushi tarazu F1β (FTZF1β)-mediated JAK-STAT signaling suppression axis in Pacific white shrimp Penaeus vannamei, the world's most produced aquaculture shrimp. We found that FtzF1β is constitutively expressed in various tissues and localizes primarily to the nucleus. Its expression increases upon pathogen exposure, with distinct patterns in viral and bacterial infections. FtzF1β functions as a transcription factor to upregulate SOCS2 transcription by directly binding SOCS2 promoter, thereby establishing a new mechanism for inhibiting the JAK-STAT pathway. Knockdown of FtzF1β using RNAi strategy upregulates immune effector genes, enhances hemocyte phagocytosis, and promotes immune defense against pathogen infection. Building on these findings, we developed an oral RNAi delivery approach using a bacterial dsRNA expression system targeting Ftz-F1β, which significantly activated the JAK-STAT pathway and improved shrimp survival upon pathogen challenge. This study advances our understanding of immune regulation in invertebrates and offers a promising strategy for disease control in aquaculture.