NUTRition, IMmune CHECKpoints, and metabolic health – Nutrim_Check

Obesity is associated with increased severity of infectious diseases. There is an urgent need to provide adapted lifestyle recommendation to reduce that risk which could be due to low grade inflammation and increased immune checkpoint (ICP) overexpression such as the PD-1/PDL1 pathway that leads to exhaustion of T-cells. Nutrim_Check is a new translational research collaborative network involving 4 groups of investigators that is organized into 6 complementary work-packages. Combining expertise in nutrition, metabolism, immunology and large-scale data analysis, our aim is to assess the interaction between NUTRition, IMmune CHECKpoints, and immune and metabolic health. Thanks to access to databases and biobanks with blood and adipose tissue samples from existing cohorts of subjects with metabolic deterioration, we will characterize obesity-related and cell and tissue-specific T cell dysfunction (ICP expression) and explore the interaction between dietary patterns, nutrients, gut microbiota (GM), metabolites and ICP modification (WP1). We will evaluate if T cell dysfunction can be rescued after dietary intervention known to improve metabolism and inflammation in a pilot study (WP2, i.e. called the pro immune diet). Mechanistic insights linking changes of T cell ICP expression will be addressed using ex vivo and in vitro models from human cells and detailed immune cell characterization will be undertaken (WP3). The infectious model of investigation will be the COVID-19, but this project extends broadly to viral infection vulnerability. Of note, an holistic and standardized mass cytometry approach will be used to obtain a detailed phenotyping of the immune populations. Patients from the pilot nutritional intervention will also be phenotyped in depth at the molecular level (metagenomics and metabolomics, WP4) and large-scale data analysis will be undertaken thanks to local expertise in biostatistic and machine learning (WP5). We will explore a novel not yet explored idea that chronic inflammatory tone due to increased expression of ICP contributes to adaptive immune evasion and sustained viral infection in dietary-related diseases. We propose this phenomenon may be fixable by nutritional amelioration in vulnerable populations such as people with obesity and metabolic diseases. Thanks to precise coordination (WP6), the project will provide information of academic and industrial interest with new information on food compounds known to broaden their spectrum of consumption, with emphasis on the immune response. The communication and dissemination Strategy will address the various target groups including the public, food, pharma and healthcare sectors and policy makers