Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE) results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD). The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure.

No abstract

Whooping cough is a highly contagious respiratory disease caused by Bordetella pertussis (Bp). The prolonged nature of whooping cough has been associated with delayed Th17 responses, which are essential to resolve the infection. Regulatory T cells (Treg) are historically immunosuppressive, but have recently been demonstrated to facilitate proper immune responses during certain infections and to occasionally adapt proinflammatory phenotypes. Because Treg and Th17 cells are considered “brothers in arms,” we evaluated the role of Tregs during immune response to B. pertussis. Here, we test the hypothesis that Tregs are crucial for generating a proinflammatory response that resolves whooping cough. We show that homeostatic lung Tregs acquire a highly proliferative Th17 phenotype during Bp infection in mice and that the frequency of this Th17-like Tresg (T17reg) population raises in parallel with Th17 influx and expansion at late phases of infection. Our data suggests that the frequency of lung T17reg may be modulated by levels of IFNa and IL-2 in the lung. Depleting Foxp3+ cells throughout Bp infection resulted in decreased MHC class II expression on dendritic and endothelial cells, suggesting reduced APC maturation. Additionally, Treg knockout lead to increased lung IL-2 levels (which may diminish Th17 differentiation/accumulation) and compromised IL-17 secretion. Moreover, infected mice lacking Treg had an increased Bp load in the lungs. Our data support Tregs facilitating and assisting Th17 immune responses to Bp to help resolve the infection.