A team at INRS makes a promising advance in the fight against chronic infections
LAVAL, QC, July 24 2025 / CNW/ – Faced with chronic infections or certain cancers, CD8+ T cells – real soldiers of the immune system – end up exhausting. They become less effective and respond less well to threats. This weakening is a major therapeutic issue, because it limits the ability of the body to resist chronic infections.
However, the team of Professor Simona Stäger at the National Institute of Scientific Research (INRS), in collaboration with her colleagues from INRS and McGill University, discovered a key player who could change the situation: the IRF-5 transcription factor. This key factor would be able to preserve the energy and vitality of these CD8+T cells, by acting directly on their metabolism.
These works, recently published in the Embo Journal journal, illustrate the importance of basic research to better understand the workings of the immune system and develop innovative therapeutic approaches.
A key ally against the exhaustion of T cells
The exhaustion of T cells is caused by several factors, including an imbalance in their internal functioning. Normally, these cells change their way of producing energy to react quickly to an infection. But when stimulation lasts too long, as in a chronic infection, their metabolism is exhausted, they produce less cytokines, chemical messengers essential to the immune response and their mitochondria, “energy power plants” of the cell, work less well, and they end up losing their effectiveness.
In this study, the research team used the LCMV Clone 13 virus, a chronic infection model, to explore the role of the IRF-5 transcription factor in CD8+T cells. Although known in other cell types, its role in these cells has so far been unexplored.
“Our results show that irf-5 acts as a real guardian of metabolism and the mitochondrial function of T cells. It helps T cells to keep their energy and their ability to fight, even in a situation of prolonged stress,” explains the main author of the study, the professor at the Inrs Simona StägerExpert in immunology of infectious diseases and vice-director of infectiopole.
Scientists discovered that the absence of IRF-5 aggravates this exhaustion. CD8+ IRF -5 deficient cells have an alteration of their lipid metabolism, an increase in mitochondrial oxidative stress and a reduction in oxidative phosphorylation – so many factors that affect their effectiveness.
A promising advance to better understand immunity
This discovery opens the way to new strategies to strengthen immunity in the context of chronic infections or cancers, where the exhaustion of T cells is also observed.
“I hope that our work will help better understand how to modulate cellular metabolism in order to support and strengthen the immune response during chronic infections or cancers. The IRF-5 transcription factor could play a key role in this approach, ”explains the first author of the study, Linh Thuy Maia graduate of a doctorate in virology and immunology at INRS and currently postdoctoral researcher at Albert Einstein College of Medicine in the United States.
The laboratory of Professor Stäger is based at the Armand-Frappier Health Center Biotechnology of INRS, the only member in North America of Pastor Network.
About the study
The article entitled Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8+ T-cells during viral infection was co -written by Linh Thuy Mai, Sharada Swaminathan, Trieu Hai Nguyen, Etienne Collette, Tania CharpentierLiseth Carmona-Pérez, Hamza Loucif, Alain LamarreKrista M Heinonen, David LanglaisJörg H Fritz, et Simona Stäger.
These research work was funded by the health research institutes of the Canada (IRSC), the Armand-Frappier Foundation and the Quebec Research Fund.
About the INRS
The INRS is a university establishment dedicated exclusively to research and training in higher cycles in strategic slots in Quebec. Since its creation in 1969, it has continued its mission to actively contribute to the economic, social and cultural development of Quebec. The Inrs ranks 1is in Quebec in research intensity. It is made up of five interdisciplinary research and training centers, located in Quebec, Montreal, in Lavalhas Varennesand in Charlevoix, which concentrate their activities in strategic sectors: Earth Earth Environment, Energy Telecommunications Materials, Urbanization Culture Society, Armand-Frappier Health Biotechnology, and sustainable ruralities (developing center). Its community has nearly 1,500 students, trainees at the postdoctorate, faculty members and staff members.
Source National Institute of Scientific Research (INRS)
Contact: Julie Robert, Communications and Public Affairs Service, National Institute of Scientific Research (INRS), [email protected](514) 971-4747
