The Genetic Mechanism Of Kruppel-like Transcription Factors KLF-1 Suppressing Innate Immunity In Caenorhabditis Elegans

Innate immunity is the first line of defense for the host to pathogens.Its homeostasis is the necessary basis for normal activities of organism.Many diseases are associated with immune disorders.Therefore,the in-depth study of immune homeostasis plays an important role in overcoming human immune diseases.Caenorhabditis elegans（C.elegans） is a well-model for studying the relationship between host and pathogen.Pseudomonas aeruginosa 14（PA14）and Caenorhabditis elegans were used to construct pathogen-host models to explore new factors affecting innate immunity.The transcriptome Sequencing（RNA-seq）was performed after wildtype worms N2 were fed with OP50 or PA14 for 24 h,respectively.The results showed that PA14 treatment could up-regulate Zinc-finger structural transcription factors.Zincfinger structural factors are very vital in organisms activities.One such family is the Kruppe-like family,whose transcription factor KLF-1 plays an important role in longevity,fatty acid metabolism,axon regeneration,oxidative stress,and mitochondrial disorders in worms.The survival experiments of worms with klf-1 RNAi exposed to PA14 revealed that worms had stronger resistance to PA14 than the control when klf-1was reduced.In order to explore the mechanism of klf-1 gene in innate immunity,the main mutants in immune pathway were used in this study,and the downstream immune genes of these pathway were labeled with Green Fluorescent Protein and their fluorescence levels after klf-1 RNAi were measured.In this study,tissue specific RNAi worms were also used to performed with klf-1 RNAi clone.As the results showed,the downstream immune genes of p38/ PMK-1 were up-regulated,and worms showed more resistance to PA14 when klf-1 was only knocked down in intestinal tissue.Therefore,KLF-1 may be a novel innate immunosuppressor.KLF-1 may be a new target for regulating innate immunity in C.elegans.KLF4,the human homologue of worms KLF-1,plays an important role in the spread of cancer cells.Whether KLF4 plays a role in human immunity will be explored in future studies.In conclusion,the study on the role KLF-1 in innate immunity in C.elegans can provide some knowledge for the treatment of human immune diseases.