摘要：SummaryCholesterol is an essential nutrient for the function of diverse biological processes and for steroid biosynthesis across metazoans. However, the role of cholesterol in immune function remains understudied. Using the nematodeCaenorhabditis elegans, which depends on the external environment for cholesterol, we studied the relationship between cholesterol and innate immunity.We found that the transporter CHUP-1 is required for the effect of cholesterol in the development of innate immunity and that the cholesterol-mediated immune response requires the nuclear hormone receptor NHR-8. Cholesterol acts through NHR-8 to transcriptionally regulate immune genes that are controlled by conserved immune pathways, including a p38/PMK-1 MAPK pathway, a DAF-2/DAF-16 insulin pathway, and an Nrf/SKN-1 pathway. Our results indicate that cholesterol plays a key role in the activation of conserved microbicidal pathways that are essential for survival against bacterial infections.Graphical AbstractDisplay OmittedHighlights•Cholesterol is required forC. elegansimmunity againstP. aeruginosainfection•Cholesterol is required during animal development for proper immunity and lifespan•CHUP-1 is required for the effect of cholesterol in defense against infection•Cholesterol acts through NHR-8 to transcriptionally regulate immune genesBiochemistry; Immunity; Microbial Metabolism
