Perception of a pathogenic signature initiates intergenerational protection.

Pender, Corinne L; Dishart, Julian G; Gildea, Holly K; Nauta, Kelsie M; Page, Emily M; Siddiqi, Talha F; Cheung, Shannon S; Joe, Larry et al. · Cell · 2025

basic_science · Level V

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Abstract

Transmission of immune responses from one generation to the next represents a powerful adaptive mechanism to protect an organism's descendants. Parental infection by the natural C. elegans pathogen Pseudomonas vranovensis induces a protective response in progeny, but the bacterial cues and intergenerational signal driving this response were previously unknown. Here, we find that animals activate a protective stress response program upon exposure to P. vranovensis-derived cyanide and that a metabolic byproduct of cyanide detoxification, β-cyanoalanine, acts as an intergenerational signal to protect progeny from infection. Remarkably, this mechanism does not require direct parental infection; rather, exposure to pathogen-derived volatiles is sufficient to enhance the survival of the next generation, indicating that parental surveillance of environmental cues can activate a protective intergenerational response. Therefore, the mere perception of a pathogen-derived toxin, in this case cyanide, can protect an animal's progeny from future pathogenic challenges.

Medical subject headings