Study in mice. A multidisciplinary team of scientists from the Institut Pasteur, the CNRS and Inserm has revealed the existence of a circuit involved in the detection and also in the regulation of the anti-inflammatory response orchestrated by different regions of the brain. This circuit detects inflammation in the blood and organizes and regulates the immune response. It represents a bidirectional connection between the brain and the immune system. The results were published in the journal Neuron .
Whenever infections or injuries occur, the immune system is activated to control the infection and repair damaged tissue. This process involves the release of pro-inflammatory mediators that inform the brain about the body’s immune status and coordinate the immune response. In response to this signal, the brain triggers a complex reaction known as "sickness behavior" whose purpose is to reallocate energy to different systems in the body. This state is associated with behavioral changes including social avoidance and lethargy, metabolic adjustments such as fever and loss of appetite, and the release of hormones such as cortisone, to increase resistance to infection while regulating immune responses.
In this study, a multidisciplinary group made up of neurobiologists and immunologists from the Institut Pasteur, Inserm and the CNRS discovered a novel circuit that the brain uses to measure levels of inflammation in the blood and, in response to this, regulate inflammation. A region of the brain stem known as the vagal complex directly senses the levels and types of inflammatory hormones in the bloodstream. This information is then transmitted to neurons in another region of the brain stem called the parabrachial nucleus , which also receives information related to pain and certain aversive or traumatic memories. In turn, these neurons activate neurons in the hypothalamus , causing a rapid increase in cortisone , a hormone with anti-inflammatory properties, in the blood.
The scientists used cutting-edge neuroscientific approaches to identify this circuit, allowing them to individually observe the neurons involved during inflammation. The experts observed how the activity of specific neurons in the parabrachial nucleus could regulate the production of white blood cells involved in the immune response. "This research demonstrates that neuronal activity in the brain alone can have a powerful effect on the development of immune responses during infection or injury. Therefore, it provides a clear example of the powerful bidirectional connection between the body and the brain. It also fuels our ambition to discover the impact of our brain on the way we interact with microbes, fight pathogens and heal wounds," explains Gérard Eberl, Head of the Microenvironment and Immunity Unit at the Institut Pasteur.
The discovery of this circuit opens new research opportunities that will jointly contribute to the fields of neurobiology and immunology: "This study gives us additional tools to better understand the impact of systemic inflammation on our brain, mood and certain neurodegenerative processes "adds Gabriel Lepousez, neurobiologist at the Perception and Memory Unit (Institut Pasteur/CNRS).
Given the established role of the parabrachial nucleus in aversive memory processes , potential infectious threats could be avoided if this circuit is reactivated with memory of past inflammatory or aversive experiences. By taking advantage of this neuroimmune communication, the immune system could benefit from the brain’s ability to predict and anticipate threats in our environment.
This research was funded by the organizations mentioned above and also by AG2R-LA MONDIALE and MTRL.
