Mechanism Of H3K4me3 Demethylase RBR-2 In Innate Immunity Of C.elegans

Caenorhabditis elegans(C.elegans)is one of the major model organisms in the biological area.Nematodes usually live with many microorganisms.Bacteria are the main food of nematodes,but most microorganisms are dangerous source of pathogens to nematodes.Pseudomonas aeruginosa is the bacterium live in soil and water which is an opportunistic human pathogen that usually causes disease in immunocompromised or traumatic individuals.Current studies have demonstrated that clinical isolates of Pseudomonas aeruginosa PA14 could kill nematodes in laboratory conditions.In the face of complex ecological environment,nematodes could protect themselves from pathogenic bacteria through the innate immune system.At present,several immune signaling pathways have been found in nematodes to participate in nematodes resistance to pathogens,including mitogen-activated protein kinase(MAPK)signaling pathway,DAF-2/DAF-16 signaling pathway and transforming growth factor-beta(TGF-β)signaling pathway.In this study,we investigated the mechanism of H3K4me3 demethylase RBR-2 in the innate immunity of C.elegans.From the study of nematode phenotype,we found that the inhibition of rbr-2 could increase the survival rate of nematodes in Pseudomonas aeruginosa PA14 infection,and the inhibition of rbr-2 against Pseudomonas aeruginosa PA14 infection was exerted in the germline.The expression of rbr-2 was decreased after nematodes infected by Pseudomonas aeruginosa PA14 for 12 h.Further mechanism studies confirmed that silenced rbr-2 up-regulates the expression of the mitochondrial stress protein HSP-60 to activate the p38 MAPK signaling pathway.The p38 MAPK signaling pathway increased the resistance of nematodes to Pseudomonas aeruginos PA14.Above all,our study demonstrated that the H3K4me3 demethylase RBR-2 was a negative regulator of the innate immunity.