The circadian clock plays a critical role in the regulation of host immune defense.However,the mechanistic basis for this regulation is largely unknown.Herein,the core clock gene cryptochromel(cryl)knockout line in Bo...The circadian clock plays a critical role in the regulation of host immune defense.However,the mechanistic basis for this regulation is largely unknown.Herein,the core clock gene cryptochromel(cryl)knockout line in Bombyx mori,an invertebrate animal model,was constructed to obtain the silkworm with dysfunctional molecular clock,and the dynamic regulation of the circadian clock on the immune responsiveness within 24h of Staphylococcus aureus infection was analyzed.We found that deletion of cryl decreased viability of silkworms and significantly reduced resistance of larvae to S.aureus.Time series RNA-seq analysis identified thousands of rhythmically expressed genes,including immune response genes,in the larval immune tissue,fat bodies.Uninfected cry1 knockout silkworms exhibited expression patterns of rhythmically expressed genes similar to wild-type(WT)silkworms infected with S.aureus.However,cry knockout silkworms exhibited a seriously weakened response to S.aureus infection.The immune response peaked at 6 and 24 h after infection,during which“transcription storms”occurred,and the expression levels of the immune response genes,PGRP and antimicrobial peptides(AMPs),were significantly upregulated in WT.In contrast,cry I knockout did not effectively activate Toll,Imd,or NF-κB signaling pathways during the immune adjustment period from 12 to 18 h after infection,resulting in failure to initiate the immune responsiveness peak at 24 h after infection.This may be related to inhibited silkworm fat body energy metabolism.These results demonstrated the dynamic regulation of circadian clock on silkworm immune response to bacterial infection and provided important insights into hostantimicrobial defensemechanisms.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.32172794 to S.-Q.X.and 31760713 to Y.-J.W.)China Postdoctoral Science Foundation(Grant No.2021M692343 to J.-F.Q.)+2 种基金Nantong Science and Technology(Grant No.JC2021073 to J.-F.Q.)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD to S.-Q.X.)the China Agriculture Research System of MOF and MARA(Grant No.CARS-18-ZJ0103 to Y.-H.S.)。
文摘The circadian clock plays a critical role in the regulation of host immune defense.However,the mechanistic basis for this regulation is largely unknown.Herein,the core clock gene cryptochromel(cryl)knockout line in Bombyx mori,an invertebrate animal model,was constructed to obtain the silkworm with dysfunctional molecular clock,and the dynamic regulation of the circadian clock on the immune responsiveness within 24h of Staphylococcus aureus infection was analyzed.We found that deletion of cryl decreased viability of silkworms and significantly reduced resistance of larvae to S.aureus.Time series RNA-seq analysis identified thousands of rhythmically expressed genes,including immune response genes,in the larval immune tissue,fat bodies.Uninfected cry1 knockout silkworms exhibited expression patterns of rhythmically expressed genes similar to wild-type(WT)silkworms infected with S.aureus.However,cry knockout silkworms exhibited a seriously weakened response to S.aureus infection.The immune response peaked at 6 and 24 h after infection,during which“transcription storms”occurred,and the expression levels of the immune response genes,PGRP and antimicrobial peptides(AMPs),were significantly upregulated in WT.In contrast,cry I knockout did not effectively activate Toll,Imd,or NF-κB signaling pathways during the immune adjustment period from 12 to 18 h after infection,resulting in failure to initiate the immune responsiveness peak at 24 h after infection.This may be related to inhibited silkworm fat body energy metabolism.These results demonstrated the dynamic regulation of circadian clock on silkworm immune response to bacterial infection and provided important insights into hostantimicrobial defensemechanisms.
