biostudies-literatureFanelli MJNIA NIH HHSNIH HHSeadi5545https://www.ebi.ac.uk/biostudies/studies/S-EPMC10699786biostudies-literatureUnknown9(49)Infection response and other immunity-linked genes (ILGs) were first named in <i>Caenorhabditis elegans</i>-based expression after pathogen challenge, but many are also up-regulated when lipid metabolism is perturbed. Why pathogen attack and metabolic changes both increase ILGs is unclear. We find that ILGs are activated when phosphatidylcholine (PC) levels change in membranes of secretory organelles in <i>C. elegans</i>. RNAi targeting of the ADP-ribosylation factor <i>arf-1</i>, which disrupts the Golgi and secretory function, also activates ILGs. Low PC limits ARF-1 function, suggesting a mechanism for ILG activation via lipid metabolism, as part of a membrane stress response acting outside the ER. RNAi of selected ILGs uncovered defects in the secretion of two GFP reporters and the accScience advancesImmunity-linked genes are stimulated by a membrane stress pathway linked to Golgi function and the ARF-1 GTPase.PMC10699786R01 AG068670P40 OD010440R56 AG068670R01 AG053355Fanelli MJWalker AKWelsh CMSmulan LJLui DSfalseImmunity-linked genes are stimulated by a membrane stress pathway linked to Golgi function and the ARF-1 GTPase.Infection response and other immunity-linked genes (ILGs) were first named in <i>Caenorhabditis elegans</i>-based expression after pathogen challenge, but many are also up-regulated when lipid metabolism is perturbed. Why pathogen attack and metabolic changes both increase ILGs is unclear. We find that ILGs are activated when phosphatidylcholine (PC) levels change in membranes of secretory organelles in <i>C. elegans</i>. RNAi targeting of the ADP-ribosylation factor <i>arf-1</i>, which disrupts the Golgi and secretory function, also activates ILGs. Low PC limits ARF-1 function, suggesting a mechanism for ILG activation via lipid metabolism, as part of a membrane stress response acting outside the ER. RNAi of selected ILGs uncovered defects in the secretion of two GFP reporters and the acc2023-01-01T00:00:00Z2023 Dec2026-05-29T11:12:00.336Z2025-02-18T23:26:05.292ZS-EPMC106997863805581510.1126/sciadv.adi5545