Serotonin is a small molecule found in organisms across the animal kingdom. This molecule plays various roles in the human body and affects many systems including the gut and central nervous system. Over recent decades, serotonin has been found to play a role in the immune system too, and appears to help regulate how immune cells respond to invasion by infectious bacteria or viruses. Various types of immune cells that can engulf foreign particles or microorganisms via a process called phagocytosis have receptors for serotonin on their cell surface and are activated when serotonin is present.

Signaling pathways associated with part of the immune system in mammals are often highly similar to pathways found in insects. Serotonin is also known to influence many processes in insects, such as appetite, sleep and reproduction, but its role in the insect’s immune system was not well understood. In particular, insects have phagocytic cells known as hemocytes and it was unknown if serotonin helps to activate these cells.

Qi, Huang et al. have now discovered that serotonin does indeed control the activity of insect hemocytes from the caterpillars of the small white butterfly (Pieris rapae) and the fruit fly (Drosophila melanogaster). The experiments showed that two distinct receptors on a hemocyte’s cell surface can detect serotonin. One of these receptors increases phagocytic activity in both insects, while the other has the opposite effect in the caterpillar and reduces this activity. Qi, Huang et al. also discovered that phagocytosis depends on which of these receptors is most common on the hemocyte cell surface, and demonstrated that insects exposed to bacteria start to produce more of the serotonin receptors that increase phagocytosis. Further experiments showed that fruit flies in which the gene for a serotonin receptor has been deleted are more vulnerable to bacterial infections due to their poor phagocytic ability.

Insects and mammals are separated by about 500 million years of evolution, and so these findings suggest that serotonin is an ancient signaling molecule that can control the immune system across the animal kingdom. The work also supports the idea that studies of the simpler immune systems of insects, including the model organisms such as D. melanogaster, can offer insight into the immune systems of humans and other animals.