CSAD inhibits excessive inflammation during viral infections through the NF-κB signaling pathway.

Studies have shown that 129 mice generate more severe inflammatory responses than C57BL/6 (B6) mice shortly after influenza virus infection. However, the mechanisms for regulation of the magnitudes and kinetics of innate immune responses in different hosts remain to be fully understood. In this study, we found that cysteine sulfinic acid decarboxylase (CSAD), an essential enzyme in the taurine synthesis pathway, inhibits excessive inflammation after viral infection. CSAD KO mice in B6 background initiate stronger inflammatory responses and are more vulnerable to viral infections, exhibiting a phenotype resembling 129 mice. Interestingly, CSAD is differentially expressed in 129 and B6 mice; CSAD is highly expressed in B6 mice than in 129 mice. CSAD inhibits the NF-κB signaling pathway during various virus infections and stimulations. CSAD directly interacts with IKKα at the kinase domain, thus limiting the fast and strong phosphorylation of IKKα and then the downstream signaling pathway. Therefore, CSAD is a novel regulator to fine-tune the intensity of the NF-κB signaling pathway.IMPORTANCEThe mechanisms by which host factors regulate the intensity of innate immune responses are important because excessive inflammatory response can be harmful to the host. CSAD, an enzyme in the taurine synthesis pathway, inhibits excessive inflammatory responses after viral infection or stimulation by interacting with IKKα of the NF-κB signaling pathway, thus limiting the downstream activation of signaling and reducing the cytokine and chemokine gene expression. Our studies reveal for the first time that CSAD plays an important role in regulating innate immune responses, adding novel regulators to the complex networks of the NF-κB signaling pathway. Furthermore, our results also help us further understand the variations in the innate immune responses among individuals and provide a novel perspective for the development of new drugs or therapies for infectious diseases.