Orphan nuclear receptor Ftz-F1L activates the NF-κB signaling pathway by promoting the transcription of dorsal in Penaeus vannamei

The orphan nuclear receptor Ftz-F1, a member of the nuclear receptor superfamily, plays broad regulatory roles in diverse biological processes. In this study, a novel Ftz-F1 homolog, designated Ftz-F1L, was identified in the Pacific white shrimp, Penaeus vannamei . Ftz-F1L possesses a canonical nuclear receptor structure, featuring the typical ZnF_C4 domain and a C-terminal ligand-binding domain. Expression profiling showed that Ftz-F1L is widely expressed in various tissues and is significantly upregulated following challenge with white spot syndrome virus (WSSV), Vibrio parahaemolyticus , or their pathogen-associated molecular patterns (PAMPs). Functional in vivo assays demonstrated that knockdown of Ftz-F1L resulted in the downregulation of multiple immune effectors (including C-type lectins, anti-lipopolysaccharide factors, lysozymes, penaeidins, and hemolin), compromised hemocyte phagocytosis, and led to increased cumulative mortality and pathogen load after infection with V. parahaemolyticus or WSSV. Mechanistic studies indicated that Ftz-F1L localized in the nucleus, directly binds to the ZnF_C4 binding motif (AAAGGTCAAC) within the Dorsal promoter, and positively regulates its transcriptional activity, thereby activating the NF-κB signaling pathway. Our findings reveal, for the first time, that Ftz-F1L activates the shrimp NF-κB pathway by directly promoting Dorsal transcription, underscoring its critical role in antibacterial and antiviral immunity. These results enhance our understanding of the functional diversity of orphan nuclear receptors in crustacean immunoregulation and identify Ftz-F1L as a potential target for disease-resistant shrimp breeding.