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The Earth’s environment is full of reactive chemicals that can cause harm to organisms. One of the most common is hydrogen peroxide, which is produced by several bacteria in concentrations high enough to kill small animals, such as the roundworm Caenorhabditis elegans . Forced to live in close proximity to such perils, C. elegans have evolved defenses to ensure their survival, such as producing enzymes that can break down hydrogen peroxide. However, this battle is compounded by other factors. For instance, rising temperatures can increase the rate at which the hydrogen peroxide produced by bacteria reacts with the molecules and proteins of C. elegans . In 2020, a group of researchers found that roundworms sense these temperature changes through special cells called sensory neurons and use this information to control the generation of enzymes that break down hydrogen peroxide. This suggests that C. elegans may pre-emptively prepare their defenses against hydrogen peroxide in response to higher temperatures so they are better equipped to shield themselves from this harmful chemical. To test this theory, Servello et al. – including some of the authors involved in the 2020 study – exposed C. elegans to a species of bacteria that produces hydrogen peroxide. This revealed that the roundworms were better at dealing with the threat of hydrogen peroxide when growing in warmer temperatures. Experiments done in C. elegans lacking a class of sensory cells, the AFD neurons, showed that these neurons increased the roundworms’ resistance to the chemical when temperatures increase. They do this by repressing the activity of INS-39, a hormone that stops C. elegans from switching on their defense mechanism against peroxides. This is the first example of a multicellular organism preparing its defenses to a chemical after sensing something (such as temperature) that enhances its reactivity. It is possible that other animals may also use this ‘enhancer sensing' strategy to anticipate and shield themselves from hydrogen peroxide and potentially other external threats. 

Cells of all kinds often wage chemical warfare against each other. Hydrogen peroxide is often the weapon of choice on the microscopic battlefield, where it is used to incapacitate opponents or to defend against attackers. For example, some plants produce hydrogen peroxide in response to infection to fight off disease-causing microbes. Individual cells have also evolved defenses to prevent or repair ‘injuries’ caused by hydrogen peroxide. These are similar across many different species. They include enzymes called catalases, which break down hydrogen peroxide, and others to repair damage. However, scientists still do not fully understand how animals and other multicellular organisms might coordinate these defenses across their cells. Caenorhabditis elegans is a microscopic species of worm that lives in rotting fruits. It often encounters the threat of cellular warfare: many types of bacteria in its environment generate hydrogen peroxide, and some can make enough to kill the worms outright. Like other organisms, C. elegans also produces catalases to defend itself against hydrogen peroxide attacks. However, it must activate its defenses at the right time; if it did so when they were not needed, this would result in a detrimental energy ‘cost’ to the worm. Although C. elegans is a small organism containing only a defined number of cells, exactly why and how it switches its chemical defenses on or off remains unknown. Schiffer et al. therefore set out to determine how C. elegans controls these defenses, focusing on the role of the brain in detecting and processing information from its environment. Experiments looking at the brains of genetically manipulated worms revealed a circuit of sensory nerve cells whose job is to tell the rest of the worm’s tissues that they no longer need to produce defense enzymes. Crucially, the circuit became active when the worms sensed E. coli bacteria nearby. Bacteria in the same family as E. coli are normally found in in the same habitat as C. elegans and these bacteria are also known to make enzymes of their own to eliminate hydrogen peroxide around them. These results indicate that C. elegans can effectively decide, based on the activity of its circuit, when to use its own defenses and when to ‘freeload’ off those of neighboring bacteria. This work is an important step towards understanding how sensory circuits in the brain can control hydrogen peroxide defenses in multicellular organisms. In the future, it could help researchers work out how more complex animals, like humans, coordinate their cellular defenses, and therefore potentially yield new strategies for improving health and longevity.