Project description
Chronic viral infection and immune ageing
Ageing is accompanied by a progressive decline in immune function, increasing susceptibility to infection, cancer and autoimmune disease. This process is known as immunosenescence and is partly driven by chronic immune activation. However, it remains poorly understood how persistent viral infections contribute to premature immune ageing, particularly within specific organs. With the support of the Marie Skłodowska-Curie Actions programme, the DECAGE project aims to investigate how chronic hepatitis B virus infection drives accelerated ageing of immune cells within the liver. Researchers will dissect the mechanisms underlying immune cell dysfunction and characterise the metabolic changes involved. Findings will be validated in human samples, advancing understanding of immune ageing with broad implications for chronic disease and healthy longevity.
Objective
Aging is a major global health issue that increases the prevalence of multimorbidity. With the ongoing demographic shift, it is critical to understand how aging heightens susceptibility to chronic disease, disability, and frailty. The immune system is now recognized as a central driver of organismal aging. Dysfunctional adaptive immune cells, particularly T cells, are key accelerators of this process and contribute to multiple age-related pathologies. Age-associated decline in immunity, or immunosenescence, leads to impaired pathogen responses, reduced immune surveillance, and increased risk of autoinflammatory and autoimmune diseases. Thus, understanding immune aging is fundamental to understanding aging as a whole.
Prolonged immune activation is a trigger of immune cell dysfunction in cancer and chronic infection. However, the impact of chronic infection on immune aging within non-lymphoid tissues, particularly the liver, remains largely unexplored. This is especially relevant because the liver plays a central role in systemic metabolism, and immune cell metabolism is a critical regulator of immune function. Hepatitis B virus (HBV) induces a unique dysfunctional—yet not exhausted—phenotype in liver-infiltrating CD8⁺ T cells, distinguishing it from other chronic viral infections.
This project will integrate chronic HBV infection, aging, and immunometabolism to test the hypothesis that persistent hepatocellular priming drives premature aging of CD8⁺ T cells, but also of CD4+ T cells and B cells. Using high-parameter flow cytometry, multiphoton intravital microscopy, and single-cell RNA sequencing, we will dissect the mechanisms underlying adaptive immune cell dysfunction. Furthermore, we will characterize the role of metabolism in the acquisition of the aging-like phenotype. Finally, access to human samples will enable direct translational validation.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology virology
- natural sciences physical sciences optics microscopy
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2025-PF
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20132 Milano
Italy
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