Servello, Francesco et al. (2021) International Worm Meeting "The AFD temperature sensing neurons adjust C. elegans defenses to match the temperature-dependent threat of hydrogen peroxide produced by bacterial pathogens"

Derosiers, Nohelly, Martin, Olivier, Fernandes, Rute, Servello, Francesco, Lindberg, Anders, Stroustrup, Nicholas, Apfeld, Javier

[International Worm Meeting, 2021]

Activation of cellular defenses can protect hosts from the macromolecular damage induced by hydrogen peroxide-the weapon of choice for many bacterial pathogens. Sensory systems can coordinate the induction of these protective host defenses, yet direct links between individual sensory mechanisms and these innate immune responses are only beginning to be understood. Understanding how sensory mechanisms regulate C. elegans defenses to bacterially produced hydrogen peroxide may reveal novel insights into how multicellular organisms coordinate their innate immune response to changing environments. We investigated how the two AFD temperature sensing neurons in Caenorhabditis elegans use temperature information to coordinate resistance to hydrogen peroxide produced by the pathogen Enterococcus faecium. We found that hydrogen peroxide was more lethal to nematodes at higher temperatures, and that at those higher temperatures the action of the AFD neurons enabled the nematodes to deal with the increased lethality of peroxides. In addition, nematodes that developed at higher temperatures induced AFD-dependent hydrogen peroxide defenses that were lasting, nearly doubling the animals' survival to subsequent peroxide exposure at lower temperature, compared to animals grown continuously at lower temperatures. Remarkably, genetic ablation of the two AFD neurons pre-induced these defenses, leading to a three-fold increase in hydrogen peroxide resistance. Through mRNA-sequencing, we found that the AFD neurons regulated the activation of a broad set of DAF-16/FOXO and SKN-1/Nrf transcriptional targets. Genetic experiments demonstrated that in response to AFD ablation, and at higher temperatures, the partially redundant action of these two transcription factors in the intestine increased the nematode's hydrogen peroxide survival. Finally, we found that these AFD-dependent mechanisms conferred resistance to hydrogen peroxide produced by the pathogen Enterococcus faecium. As E. faecium grows in a temperature-dependent manner and produces hydrogen peroxide in a growth-dependent manner, we propose that this sensory system enables the nematodes to use temperature information to predict the likelihood of encountering bacterially produced hydrogen peroxide and adjust their innate immune defenses to match that threat.