Lung-gut axis: Inter-organ Communication during Acute Respiratory Infection

Influenza virus infection is one of the most common respiratory diseases. Symptoms of influenza include fever, cough, stuffy nose, body aches, headache, and fatigue. Additionally, patients may experience gastrointestinal symptoms such as nausea, vomiting, and diarrhoea. Yet, the reason for these clinical signs is still not clear. During acute respiratory infection, immune cells release inflammatory mediators at the site of infection that activate peripheral nerves extremities and lead to brain activation, without migration of the virus into the brain. Brain activation induces in return an anti-inflammatory response mediated by peripheral nerves which release neurotransmitters and neuropeptides dampening the immune response in the lungs. Interestingly, these pathways are not lung privileged, but also innervate other organs such as the gastro-intestinal tract. Within the intestine, the enteric nervous system (ENS) is a complex network of neurons and glia that controls many digestive functions (contraction/relaxation of the intestine, enzymes secretion). Although the ENS can function independently from the brain, these two organs are interconnected by neuronal
fibers and together coordinate the intestinal physiology. I thereby hypothesize that peripheral nerves' activation during influenza virus infection could be responsible for the observed gastrointestinal symptoms. In my project, I will test this hypothesis using a mouse model of influenza virus infection. I will implement multiscale and cutting-edge technologies in neuroscience to be able to register, identify and manipulate neurons in different organs. This analysis will help understanding the mechanisms underlying the multi-organ symptoms observed during acute respiratory infection and its impact on neuronal circuits at the level of the whole organism.