• Contributed by Troy Shirangi

Sick Behaviors

I arrive at home from work to find my five-year-old laying on the couch watching cartoons. Instantly I can tell he’s not himself. Usually when I walk through the door, he’ll run into my arms, raving about some exciting thing that happened in his day. But this time, he doesn’t even look my way. He lays there droopy, listless and dejected. It’s obvious that he’s sick.

It’s nothing remarkable to say that a person’s behavior can tell us when they’re feeling sick. But the reason why we show the behaviors that we do when we're feeling ill is a curious thing to wonder about.

Intuitively, we might think that the behaviors connected to illness are nothing more than passive side-effects from the body’s immune response. As our body fights an infection, our resources dwindle, so we naturally become lethargic and depressed. However, some scientists have suggested that these behaviors are in fact programmed, organized strategies that facilitate the body’s ability to combat an infection.

Benjamin Hart, a biologist at University of California, Davis, wrote an influential article on this topic in the late 1980s, focusing on the fever response to infection in animals. Hart argued that the depression and loss of appetite associated with a fever were probably induced by the body to relieve the increased metabolic costs that result from heightened body temperature. The behaviors of sick animals, he posited, “evolved as adaptive strategies of fighting infectious diseases when medical care was nonexistent.”

If the behaviors of sick animals are indeed adaptive strategies to infection, its mechanistic basis becomes a fascinating avenue of study. How does an infection communicate with the nervous system to induce a change in behavior? Despite how different the immune and nervous systems are, could they be responding to infection through similar molecular mechanisms?

A paper published recently in eLife has shed light onto these questions. Leopold Kurz and his colleagues in Julien Royet’s laboratory at University of Marseille in France cracked the problem open using the genetic workhorse—that is, fruit fly—Drosophila.

Flies, like other animals, are susceptible to infections. And like us, flies will generate not only an immune response to the infection, but also a set of stereotypical changes in behavior. A female fly, for instance, will attempt to limit the impact of a bacterial infection by reducing the number of eggs she lays. Kurz, Royer and their teammates were curious to find out how a bacterial infection could cause a female fly to change her egg laying behavior. What they found was a big surprise.

The researchers discovered a small group of neurons in the nervous system of female flies that produce a chemical called octopamine. These neurons suppress the female’s ability to lay eggs. It turns out that a bacterial infection will stimulate these neurons, thereby causing the female to lay fewer eggs.

The real shocker came, however, when Kurz and his coworkers dug deeper into the molecular mechanisms that control this process. The team discovered that flies were using a molecule called NF-Kappa-B to activate the octopamine neurons in response to a bacterial infection.

NF-Kappa-B, it turns out, is no stranger to science. It got its claim-to-fame decades ago for its role in activating the immune system during an infection. Just about every animal on the planet that has an immune system has an NF-Kappa-B. Remarkably, the very same molecule was being used separately by the nervous system to respond to a pathogen. It’s as if flies have a pathway in the nervous system for ‘behavioral immunity,’ a term coined some years ago by Jacobus de Roode and Thierry Lefevre.

“One wouldn’t necessarily expect the fly’s neurons and immune cells to use the same gene in triggering a response to an infection,” says Troy Shirangi, a biologist at Villanova University. “They’re totally different cells, in totally different tissues, doing totally different things. Yet they’re using the same gene to elicit a response.”

It’s as if nature was being economical; as if it were easier for the nervous system to reuse a strategy that was in place and working in the immune cells than to evolve a new one.

Whether similar mechanisms are at play in the sickness behaviors of other animals, time will only tell. But nevertheless these findings are a big step forward in the molecular and neural mechanisms that govern how we alter our behaviors in response to illness.