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. 2025 Feb 6;188(3):594-605.e10.
doi: 10.1016/j.cell.2024.11.026. Epub 2024 Dec 24.

Perception of a pathogenic signature initiates intergenerational protection

Corinne L Pender  1 , Julian G Dishart  2 , Holly K Gildea  2 , Kelsie M Nauta  3 , Emily M Page  1 , Talha F Siddiqi  1 , Shannon S Cheung  1 , Larry Joe  4 , Nicholas O Burton  3 , Andrew Dillin  5
Affiliations

Perception of a pathogenic signature initiates intergenerational protection

Corinne L Pender et al. Cell. .

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.

Keywords: C. elegans; CYSL-2; MDT-15; Pseudomonas; SKN-1; cyanide; intergenerational inheritance; pathogen sensing; volatile response; β-cyanoalanine.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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