Penaeus monodon IKKs Participate in Regulation of Cytokine-Like System and Antiviral Responses of Innate Immune System

Abstract

The IKK-NF-κB signaling cascade is one of the crucial responsive mechanisms in inflammatory and immune responses. The key kinase proteins called inhibitor of kappa B kinases (IKKs) serve as the core elements involved in cascade activation. Here, the complete ORFs of IKK homologs, PmIKK β , PmIKK ε 1 , and PmIKK ε 2 , from the black tiger shrimp Penaeus monodon were identified and characterized for their functions in shrimp antiviral responses. The PmIKK transcripts were widely expressed in various examined tissues and the Pm IKKε protein was detected in all three types of shrimp hemocytes. Only the PmIKK ε 1 and PmIKK ε 2 were responsive to white spot syndrome virus (WSSV), yellow head virus (YHV) and a bacterium Vibrio harveyi infection, while the PmIKK β exhibited no significant response to pathogen infection. On the contrary, suppression of PmIKK β and PmIKK ε by dsRNA-mediated RNA interference (RNAi) resulted in a rapid death of WSSV-infected shrimp and the significant reduction of an IFN-like PmVago4 transcript. Whereas, the mRNA levels of the antimicrobial peptides, ALFPm3 and CrustinPm5 , and a transcription factor, PmDorsal were significantly increased, those of ALFPm6, CrustinPm1, CrustinPm7, PmVago1, PmRelish , and PmCactus were unaffected. Overexpression of Pm IKKβ and Pm IKKε in HEK293T cells differentially activated the NF-κB and IFNβ promoter activities, respectively. These results suggest that the Pm IKKβ and Pm IKKε may act as common factors regulating the expression of immune-related genes from various signaling pathways. Interestingly, the Pm IKKs may also contribute a possible role in shrimp cytokine-like system and cross-talking between signaling transductions in innate immune responses.

Penaeus monodon Interferon Regulatory Factor (PmIRF) Activates IFNs and Antimicrobial Peptide Expression via a STING-Dependent DNA Sensing Pathway

“…Together with previous findings on the components of the cytosolic DNA sensing pathway in shrimp ( Pm DDX41, Pm STING, Pm IKKs, Pm IRF, and Pm Vago) ( 20 , 42 , 56 ), we propose a model of how these proteins interact in the cytosolic DNA sensing pathway to activate the antiviral immune response in P. monodon ( Figure 7 ). Possibly during infection with the DNA virus WSSV, dsDNA is detected and bound by the DNA sensor Pm DDX41, which forms a complex with Pm STING that acts via TBK–IKK–IRF3 to induce the IFN response.…”