The Function And Mechanism Of Retinal And Acetaldehyde In Antiviral Innate Immunity

The innate immune system recognizes pathogen-associated molecular patterns(PAMPs)via a number of pattern recognition receptors(PRRs),which activates specific signaling pathways.Viral nucleic acids are important pathogen-associated molecular patterns.After infection of DNA virus,cytosolic DNA can be sensed by c GAS.After recognition of DNA,c GAS catalyzes the synthesis of cyclic GMP-AMP(c GAMP)from ATP and GTP,which in turn binds to and activates an endoplasmic reticulum(ER)-located protein called MITA.MITA translocates to the Glogi and activates TBK1,TBK1 then phosphorylates IRF3.IRF3 dimerizes and enters the nucleus,which triggers the production of type I interferons and the transcription of effector genes involved in inflammatory responses.In this study,we revealed the function and mechanism of retinal and acetaldehyde in innate immunity.First of all,we screened hundreds of molecule metabolic compounds to identify their abilities to regulate ISRE activation by reporter assays.q PCR experiments indicated that retinal negatively regulated HSV-1/Se V-induced transcription of downstream genes in a dose-dependent manner.In addition,the phosphorylation of MITA,TBK1 and IRF3 induced by HSV-1 was inhibited by retinal.However,retinal had no effect on host defense against viral infection in vivo.We also found that acetaldehyde inhibited the expression of virus-and transfected DNA-triggered induction of downstream genes in a dose-dependent manner,but had no marked effect on c GAMP-induced signaling pathways.Reporter assays indicated that acetaldehyde inhibited the activation of c GAS-MITA-induced ISRE.What's more,acetaldehyde impaired the ability of c GAS to synthesize c GAMP.Finally,we found that acetaldehyde inhibited the induction of serum cytokines following infection of DNA viruses HSV-1 rather than RNA viruses Se V.Taken together,our findings suggested that retinal and acetaldehyde could inhibit antiviral innate immune response in vitro.Acetaldehyde could negatively regulate the immune response mediated by c GAS-MITA singnaling pathway.This study may provide a target for the development of drugs in antiviral innate immunity.