Detection of bacteria by neurons: modalities and consequences for fly behaviour – BACNEURODRO

Since eukaryotes live in an environment heavily contaminated by microorganisms, it is not surprising that they have forged, over the times, extremely complex and intimate relationships between them. It also expected that eukaryotes have developed mechanisms to perceive the presence of bacteria and to adapt their immune response, their physiological status or even their behavior accordingly. Many reports have shown that bacteria can interact with eukaryote nervous system, either for the benefit of the microbe that alters the host's behavior or to the benefit of the host that adapts its behavior to the infection. However, the molecules and mechanisms underlying the dialog between bacteria and neurons of their hosts are, in most cases, not identified and their mode of action is still poorly understood.
Here, we specifically examine the effects of one identified bacteria cell wall component, called peptidoglycan (PGN) on the host's nervous system. While PGN is known to be an integral part of bacterial call wall, it can elicit a range of reactions in higher animals, the most prominent one being the activation of the antibacterial immune response upon its detection by the infected sentinel proteins. In Drosophila, we have recently demonstrated that central neurons can detect PGN, inducing a series of behavioral changes which reduce the consequences of infection (1). PGN is detected by octopaminergic neurons associated with female’s reproductive organs. In turn, these neurons inhibit the egg-laying behavior of infected females. We have identified proteins expressed in these neurons which enable them to sense PGN and to modulate its effects on neurons. Interestingly, one of these proteins is not only expressed into neurons regulating oviposition but also into external gustatory neurons. Given the unexpected distribution of these PGN receptors outside the immune tissues, we wonder whether what we observed at the level of oviposition is a phenomenon strictly related to the ovaries or whether it affects other higher functions of the flies such as feeding. Our proposal takes advantage of the power of Drosophila genetics to dissect at the molecular level, the mechanisms by which neurons are sensing PGN and how this interaction is translated into behavioral changes for the host. More specifically, this proposal is aimed at (1) further dissecting how PGN modulates octopaminergic neurons activity in relation to oviposition and (2) at examining the generality of this neuronal "immunocompetence" by focusing on the peripheral taste system that also express these PGN sensors. Recent results showing that PGN sensors and transporters are expressed in the mouse brain and that mice deficient in PGN-sensing proteins exhibit social behavioral alterations (2) let us believe that the mechanisms that we propose to study in this proposal using the Drosophila model could also exist in mammals.