Eucaryotes live in diversified ecological niches that, while variable in terms of physical and chemical characteristics, are all colonized by microorganisms such as bacteria, viruses or fungi. It follows that, from the earliest stages of their development until their death, animals interact for better or for worse with these co-inhabitants. For the better, as microbes can positively impact various physiological parameters of the host such as fecundity, longevity, and growth, to name but a few. For worse, since, obviously, some of these microbes can negatively affect the host and can even sometimes be life-threatening for them. To defend themselves, eucaryotes have developed immune strategies to identify surrounding microorganisms and trigger ad hoc responses that eradicate invaders and ensure the integrity and fitness of the host and its progeny. Recent studies highlight the benefits of bringing neurons into the complex host–microbe interaction game. Sensory neurons play a role in identifying microbes and, thus, in distinguishing beneficial ones to live with from other, potentially pathogenic, ones to avoid. In contrast, host neurons can be hijacked by microorganisms and microbe-derived products to ease their proliferation within infected animals. In addition, the nervous system’s perception of a microbial threat may allow the host to modify its behavior to reduce the consequences of the infestation on itself and its offspring.

As neuroscientists and immunologists continue to uncover molecules acting across both systems and genetic interactions between them, it becomes clear that the immune and the neuronal systems share many components, and cooperate at many different levels to allow an animal to live in harmony with its exogenous and endogenous microbes. Using its powerful collection of genetic and genomic tools, we used Drosophila to understand how immune and neuronal mechanisms cooperate to enable flies to protect themselves from pathogenic microbes or sometimes to take advantage of the microorganisms they live with.