RIOK-1 is a suppressor of the p38 MAPK innate immune pathway in Caenorhabditis elegans

Abstract

The homeostasis of innate immunity is critical for the primary defense mechanism against infection and regulating immune response in metazoans It has been proven that aberrant up-regulation of innate immune signaling pathways can be detrimental to the host The p38 MAPK/PMK-1 innate immune signaling pathway has been demonstrated to play essential roles in cellular defenses against numerous infections in metazoans including Caenorhabditis elegans However the negative regulators that maintain the homeostasis of this important innate immune pathway remain largely understudied By screening a focused kinome RNAi library of C elegans we identified a human RIO kinase homolog RIOK-1 as a novel suppressor of the p38 MAPK/PMK-1 signal pathway We showed that the suppression of riok-1 confers resistance to Aeromonas dhakensis infection in C elegans Using riok-1 reporter worms and qRT-PCR we found the expression levels of riok-1 were significantly up-regulated in A dhakensis infected worms With genetic epistasis analysis of many immune pathways in C elegans we also discovered that riok-1 acts on the upstream of the p38 MAPK/pmk-1genetic pathway Moreover the suppression of riok-1 enhanced the activity of p38 MAPK suggesting that riok-1 is a negative regulator of this innate immune pathway in C elegans The epistatic results also put riok-1 upstream of skn-1 which encodes a p38 MAPK downstream transcription factor participates as an upstream activator to riok-1 and serves as a feedback loop to the p38 MAPK pathway during A dhakensis infection In conclusion we proposed riok-1 is a novel innate immune suppressor and a negative feedback loop model involving p38 MAPK cascade SKN-1 and RIOK-1 in C elegans

Date of Award	2018 Sept 25
Original language	English
Supervisor	Chang-Shi Chen (Supervisor)