Temperature perception by ER UPR promotes preventive innate immunity and longevity

Microbial infectivity increases with rising environmental temperature, heightening the risk of infection to host organisms. The host's basal immunity is activated accordingly to mitigate upcoming pathogenic threats; still, how animals sense temperature elevation to adjust their preventive immune response remains elusive. This study reports that high temperature enhances innate immunity differently from pathogen infection. Unlike pathogen invasion requiring the mitochondrial unfolded protein response (UPR), high temperature engages the endoplasmic reticulum (ER) UPR to trigger the innate immune response. Furthermore, chronic activation of the XBP-1 UPR branch represses nucleolar ribosome biogenesis, a highly energy-consuming process, leading to lipid accumulation. The subsequent increase in oleic acid promotes the activation of the PMK-1 immune pathway. Additionally, ribosome biogenesis was identified as a regulator of longevity, wherein its impact is dependent on lipid metabolism and innate immunity. Collectively, our findings reveal the crucial role of ER-nucleolus crosstalk in shaping preventive immune responses and lifespan regulation.