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Month: March 2020

Influenza: combating bacterial superinfection with the help of the microbiota

Posted on by Graziella Cara

Section of lungs infected with influenza virus with a major inflammation which results in a marked infiltration of neutrophil polynuclear cells, dark cells. © Inserm/Si-Tahar, Mustapha

Researchers from the CNRS, INSERM, the Institut Pasteur de Lille, INRAE (France) and from Brazilian (Belo Horizonte), Scottish (Glasgow) and Danish (Copenhagen) laboratories have shown for the first time in mice that perturbation of the gut microbiota caused by the influenza virus favours secondary bacterial superinfection. Published in Cell Reports on March 3, 2020, these results open up new prospects for the prevention and treatment of bacterial pneumonia, a major cause of death in elderly or vulnerable people infected with the influenza virus.

Influenza and its complications continue to be a significant public health concern as well as a major social and economic burden. Vaccination campaigns, together with the discovery of new antiviral therapies, provide preventive and therapeutic solutions. However, impairment of defence mechanisms against secondary bacterial infections, which considerably worsen the clinical picture of people with influenza, remains a major problem.

Specializing in the field of pulmonary immunity, a team led by François Trottein, a CNRS researcher at the Lille Centre for Infection and Immunity (CNRS/INSERM/Institut Pasteur de Lille/University of Lille/CHU Lille), focused on the gut microbiota, well known for their key role in many physiological processes, including immune defence mechanisms. Scientists have shown that, in mice, influenza temporarily alters the composition and metabolic activity of the gut microbiota, probably due to reduced food consumption during illness. During influenza, the production of short-chain fatty acids by the bacteria of the microbiota is also diminished. The team has now shown that these fatty acids remotely favour the bactericidal activity of macrophages present in the lungs.  Perturbation of the intestinal microbiota by influenza thus compromises lung defences, particularly against Streptococcus pneumoniae, the leading cause of bacterial pneumonia in humans.

The researchers also showed that this sensitivity to bacterial superinfection can be corrected by treatment with acetate, one of the main short-chain fatty acids produced by the microbiota. Their work could have practical applications for the well-being of infected patients, who would be better protected against influenza-related complications.  This work was made in collaboration with scientists from the Micalis Institute (INRAE/AgroParistech/Université Saclay), the Lille Inflammation Research International Center (INSERM/Université de Lille/CHU Lille), the Laboratory of Design and Application of Bioactive Molecules (CNRS/University of Strasbourg), the Molecular Virology and Immunology Unit (INRAE) and GenoScreen (Lille), the Universidade Federal de Minas Gerais (Belo Horizonte, Brazil), the Institute of Molecular, Cell and Systems Biology (Glasgow, Scotland) and the Department of Pharmacology (University of Copenhagen, Denmark). This discovery represents a major breakthrough in the understanding of the mechanisms behind bacterial superinfections in influenza patients. It could lead to the development of new nutritional and/or therapeutic strategies to better control bacterial infections.

The origin of satiety: brain cells that change shape after a meal

Posted on by Graziella Cara

POMC neurons (orange dots) in the hypothalamus of a mouse, located at the base of the brain. Photo taken from a mouse using a confocal microscope.© Danaé Nuzzaci / CNRS / CSGA

You just finished a good meal and are feeling full? Researchers from the CNRS, Inrae, University of Burgundy, Université de Paris, Inserm, and University of Luxembourg1 have just revealed the mechanisms in our brains that lead to this state. They involve a series of reactions triggered by a rise in blood glucose levels. This study, which was conducted on mice, is published in Cell Reports on 3 March 2020.

The neuronal circuits in our brain governing feelings of hunger and satiety can modify their connections, thereby adjusting feeding behaviour to living conditions and maintaining a balance between food intake and calorie expenditure. Scientists suspect that this plasticity could be altered for obese subjects.

In a new study conducted on mice, a team led by Alexandre Benani, a CNRS researcher at the Centre for Taste and Feeding Behavior (CNRS/Inrae/University of Burgundy/AgroSup Dijon), has shown that these circuits are activated on the time scale of a meal, subsequently regulating feeding behaviour. However, this activation does not occur through a change in the circuit’s “connections.”

Remodelling of the satiety circuit of POMC neurons after a balanced meal. Red box: area corresponding to the photo at right.© Alexandre Benani / CNRS / CSGA

Scientists focused on POMC neurons in the hypothalamus, located at the base of the brain, which are known for limiting food intake. They are connected to a large number of neurons from other parts of the brain, with the connections of this circuit being malleable: they can be made and unmade very quickly based on hormonal fluctuations. Researchers observed that this neuronal circuit is not modified after a balanced meal, but that other nerve cells associated with POMC neurons, known as astrocytes, actually change form.

Astrocytes are star-shaped nerve cells that were first studied for their supporting role with respect to neurons. Under usual conditions, they sheathe POMC neurons and act somewhat like brake pads by limiting their activity. After a meal, blood glucose levels (glycaemia) temporarily increase, with astrocytes detecting this signal and retracting in less than one hour: once this “brake” is released, POMC neurons are activated, ultimately promoting the feeling of satiety.

Surprisingly, a meal that is high in fats does not lead to this remodelling. Does this mean that lipids are less effective in satisfying hunger? The scientists are trying to determine whether they trigger satiety through another circuit. It also remains to be seen whether sweeteners have the same effects, or whether they lure the brain by providing an addictive sensation of sweetness without satisfying hunger.

 

1 The study was led by the Centre for Taste and Feeding Behavior (CNRS/Inrae/University of Burgundy/Agrosup Dijon), in close collaboration with colleagues from the Institute of Molecular and Cellular Pharmacology (CNRS/Université Côte d’Azur), Institute for Functional Genomics (CNRS/Inserm/ University of Montpellier), and University of Luxembourg, along with contributions from l’Unité de biologie fonctionnelle et adaptative (CNRS/Université de Paris) and Institute of Psychiatry and Neuroscience of Paris (Inserm/Université de Paris).

 

 

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