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CORDIS

Immunometabolic regulation of the host response to viral infection in the context of obesity

Description du projet

Le lien entre l’obésité et les infections virales graves

Les personnes obèses présentent un risque nettement plus élevé de développer des symptômes plus aigus liés à une infection virale. Nous ignorons la raison précise de ce phénomène. Des études sur des souris ont révélé que les spécimens obèses développaient une perte profonde et progressive de graisse et de muscle en réponse à une infection virale chronique. Dans ce contexte, le projet Virobe soutenu par le programme Actions Marie Skłodowska-Curie identifiera les mécanismes à l’origine de cette perte de tissus marquée et progressive chez les souris obèses infectées. Plus précisément, il vérifiera si la perte de tissu observée pendant l’infection virale résulte d’une homéostasie perturbée du glucose, de perturbations des fonctions des macrophages et de profils anormaux de cytokines relevés dans le contexte de l’obésité. Les résultats mettront en lumière de potentielles stratégies thérapeutiques visant à améliorer le bilan de la maladie virale chez les personnes obèses.

Objectif

Chronic viral diseases are of significant concern to the public health due to lack of effective vaccines and paucity of potent anti-viral medication. Notably, individuals with obesity exhibit higher morbidity and mortality due to viral diseases. However, what specific mechanisms underlie the confounding effects of obesity on the overt outcome of viral infections remains poorly understood. In pre-clinical studies, I found that obese mice developed profound and progressive loss of fat and muscle in response to chronic viral infection, while metabolically healthy animals showed only transient and significantly milder manifestation of tissue wasting in response to the virus. In this proposal, I aim to identify the mechanisms driving this marked and progressive tissue wasting in infected obese mice. Inflammation and disrupted glucose homeostasis have been implicated to play a role in tissue wasting. I hypothesize that the profound tissue wasting during viral infection results from uncontrolled glucose homeostasis, perturbations in macrophage functions and from abnormal cytokine profiles observed in the context of obesity. I will test my hypothesis using high-fat diet-induced mouse model of obesity infected with chronic strain of the lymphocytic choriomeningitis virus. I will test the involvement of cytokines, macrophages as well as of glucose homeostasis in the progressive wasting in infected obese animals and evaluate if there is a crosstalk between these three factors during infection in an obese host. This project will generate critical knowledge to address why host response to virus is disrupted in the context of obesity and identify potential therapeutic strategies for improving the outcome of viral diseases such as tissue wasting in this metabolic disease. Moreover, this study will highlight the crosstalk between the immune system and body metabolism during infection and will help to better understand the processes underlying immunity to pathogens.

Régime de financement

MSCA-PF - MSCA-PF

Coordinateur

KOBENHAVNS UNIVERSITET
Contribution nette de l'UE
€ 214 934,40
Adresse
NORREGADE 10
1165 Kobenhavn
Danemark

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Région
Danmark Hovedstaden Byen København
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
Aucune donnée