Mitochondrial UPR negatively regulates wounding-induced innate immune response in C. elegans epidermis

Abstract

Tissue damage elicits a rapid innate immune response that is essential for efficient wound healing and survival of metazoans. It is well known that p38 MAPK kinase, TGF-{beta}, and hemidesmosome signaling pathways have been involved in wounding-induced innate immunity in C. elegans. Here, we find that loss of function of ATFS-1 increased innate immune response while an elevated level of mitochondrial unfolded protein response (mitoUPR) inhibits the innate immune response upon epidermal wounding. Epidermal wounding triggers the nucleus export of ATFS-1 and inhibits themitoUPR in C. elegans epidermis. Moreover, genetic analysis suggests that ATFS-1 functions upstream of the p38 MAP kinase, TGF-{beta} and DAF-16 signaling pathways in regulating AMPs induction. Thus, our results suggest that the mitoUPR function as an intracellular signal required to fine-tune innate immune response after tissue damage. Highlights-- ATFS-1 inhibits the wounding-induced innate immune response in C. elegans -- mitoUPR inhibits wounding-induced innate immune response -- Epidermal wounding induces downregulation of ATFS-1 in the epidermis -- mitoUPR acts upstream of p38MAPK and TGF-{beta} pathways to regulate innate immunity