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

Project description

The link between obesity and severe viral infections

Humans who are obese have significantly higher risk of developing more severe symptoms due to viral infection. The reason for this is not well understood. Studies on mice found that the obese mice developed profound and progressive loss of fat and muscle in response to chronic viral infection. In this context, the Marie Skłodowska-Curie Actions project Virobe will identify the mechanisms driving this marked and progressive tissue wasting in infected obese mice. Specifically, it will test whether that the tissue wasting during viral infection results from disrupted glucose homeostasis, perturbations in macrophage functions and from abnormal cytokine profiles observed in the context of obesity. The findings will shed light on potential therapeutic strategies aiming at improving the outcome of viral disease in obese persons.

Objective

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.

Funding Scheme

MSCA-PF - MSCA-PF

Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution
€ 214 934,40
Address
NORREGADE 10
1165 Kobenhavn
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data