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Protecting Immune Cells from Exhaustion
Protecting Immune Cells from Exhaustion

Yahoo

time24-07-2025

  • Health
  • Yahoo

Protecting Immune Cells from Exhaustion

INRS research team makes a promising breakthrough in the fight against chronic infections LAVAL, QC, July 24, 2025 /CNW/ - In fighting chronic infections or certain cancers, CD8+ T cells—the immune system's frontline soldiers—eventually become exhausted. They lose effectiveness and respond less efficiently to threats. This weakening is a major therapeutic challenge, as it limits the body's ability to fight chronic infections. However, the team of Professor Simona Stäger at Institut national de la recherche scientifique (INRS), in collaboration with colleagues from INRS and McGill University, has identified a key game changer: IRF-5. This transcription factor appears to preserve the energy and vitality of CD8+ T cells by acting directly on their metabolism. These findings, recently published in The EMBO Journal, highlight the importance of fundamental research in understanding the immune system and developing innovative therapeutic approaches. A Key Ally Against T Cell Exhaustion T cell exhaustion is caused by several factors, including an imbalance in internal cell functioning. Normally, T cells shift their energy production to respond quickly to infection. But when they are stimulated for too long—as during chronic infections—their metabolism becomes depleted. They produce fewer cytokines (chemical messengers essential to the immune response), their mitochondria (the cell's energy centres) function less efficiently, and they ultimately lose their effectiveness. In this study, the team used the LCMV Clone 13 virus, a model of chronic infection, to explore the role of IRF-5 in CD8+ T cells. While the role of IRF-5 in other cell types is well known, its function in these immune cells had not been explored until now. "Our results show that IRF-5 acts as a guardian of T cell metabolism and mitochondrial function. It helps T cells maintain their energy and ability to fight, even under prolonged stress."—Simona Stäger, INRS professor and senior author of the study, expert in immunology of infectious diseases, and Vice-director of Infectiopole. The researchers found that the absence of IRF-5 worsens exhaustion. CD8+ T cells lacking IRF-5 showed disrupted lipid metabolism, increased mitochondrial oxidative stress, and reduced oxidative phosphorylation—all factors that impair their function. A Promising Step Toward Better Understanding Immunity This discovery opens the door to new strategies for boosting immunity to chronic infections or cancers, where T cell exhaustion is also observed. "I hope our work will help us better understand how to modulate cellular metabolism to support and enhance immune responses during chronic infections or cancer. IRF-5 transcription factor could play a key role in this approach."—Linh Thuy Mai, lead author of the study, former PhD student in virology and immunology from INRS, currently a postdoctoral fellow at Albert Einstein College of Medicine, United States. Professor Stäger's laboratory is based at the INRS Armand-Frappier Santé Biotechnologie Research Centre, the sole North American member of the Pasteur Network About the Study The article, titled Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8+ T-cells during viral infection, was co-authored by Linh Thuy Mai, Sharada Swaminathan, Trieu Hai Nguyen, Etienne Collette, Tania Charpentier, Liseth Carmona-Pérez, Hamza Loucif, Alain Lamarre, Krista M. Heinonen, David Langlais, Jörg H. Fritz, and Simona Stäger. This research was funded by the Canadian Institutes of Health Research (CIHR), the Armand-Frappier Foundation, and Fonds de recherche du Québec. About INRS INRS is an academic institution dedicated exclusively to graduate research and training in strategic sectors in Quebec. Since 1969, as per its mission, it has actively contributed to Quebec's economic, social, and cultural development. INRS ranks first in Quebec in research intensity. It is made up of five interdisciplinary research and training centres located in Quebec City, Montreal, Laval, and Varennes, and Charlevoix, which focus their efforts on strategic sectors: water, earth, and environment (Eau Terre Environnement Research Centre); energy, materials, and telecommunications (Énergie Matériaux Télécommunications Research Centre); urbanization, culture, and society (Urbanisation Culture Société Research Centre); and health and biotechnology (Armand-Frappier Santé Biotechnologie Research Centre), and Ruralités durables (a center currently under development). Its community includes nearly 1,500 members, including students, postdoctoral fellows, faculty members, and staff. SOURCE Institut National de la recherche scientifique (INRS) View original content to download multimedia: Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data

Protecting Immune Cells from Exhaustion Français
Protecting Immune Cells from Exhaustion Français

Cision Canada

time24-07-2025

  • Health
  • Cision Canada

Protecting Immune Cells from Exhaustion Français

INRS research team makes a promising breakthrough in the fight against chronic infections LAVAL, QC, July 24, 2025 /CNW/ - In fighting chronic infections or certain cancers, CD8+ T cells—the immune system's frontline soldiers—eventually become exhausted. They lose effectiveness and respond less efficiently to threats. This weakening is a major therapeutic challenge, as it limits the body's ability to fight chronic infections. However, the team of Professor Simona Stäger at Institut national de la recherche scientifique (INRS), in collaboration with colleagues from INRS and McGill University, has identified a key game changer: IRF-5. This transcription factor appears to preserve the energy and vitality of CD8+ T cells by acting directly on their metabolism. These findings, recently published in The EMBO Journal, highlight the importance of fundamental research in understanding the immune system and developing innovative therapeutic approaches. A Key Ally Against T Cell Exhaustion T cell exhaustion is caused by several factors, including an imbalance in internal cell functioning. Normally, T cells shift their energy production to respond quickly to infection. But when they are stimulated for too long—as during chronic infections—their metabolism becomes depleted. They produce fewer cytokines (chemical messengers essential to the immune response), their mitochondria (the cell's energy centres) function less efficiently, and they ultimately lose their effectiveness. In this study, the team used the LCMV Clone 13 virus, a model of chronic infection, to explore the role of IRF-5 in CD8+ T cells. While the role of IRF-5 in other cell types is well known, its function in these immune cells had not been explored until now. "Our results show that IRF-5 acts as a guardian of T cell metabolism and mitochondrial function. It helps T cells maintain their energy and ability to fight, even under prolonged stress." — Simona Stäger, INRS professor and senior author of the study, expert in immunology of infectious diseases, and Vice-director of Infectiopole. The researchers found that the absence of IRF-5 worsens exhaustion. CD8+ T cells lacking IRF-5 showed disrupted lipid metabolism, increased mitochondrial oxidative stress, and reduced oxidative phosphorylation—all factors that impair their function. A Promising Step Toward Better Understanding Immunity This discovery opens the door to new strategies for boosting immunity to chronic infections or cancers, where T cell exhaustion is also observed. "I hope our work will help us better understand how to modulate cellular metabolism to support and enhance immune responses during chronic infections or cancer. IRF-5 transcription factor could play a key role in this approach." — Linh Thuy Mai, lead author of the study, former PhD student in virology and immunology from INRS, currently a postdoctoral fellow at Albert Einstein College of Medicine, United States. About the Study The article, titled Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8+ T-cells during viral infection, was co-authored by Linh Thuy Mai, Sharada Swaminathan, Trieu Hai Nguyen, Etienne Collette, Tania Charpentier, Liseth Carmona-Pérez, Hamza Loucif, Alain Lamarre, Krista M. Heinonen, David Langlais, Jörg H. Fritz, and Simona Stäger. This research was funded by the Canadian Institutes of Health Research (CIHR), the Armand-Frappier Foundation, and Fonds de recherche du Québec. About INRS INRS is an academic institution dedicated exclusively to graduate research and training in strategic sectors in Quebec. Since 1969, as per its mission, it has actively contributed to Quebec's economic, social, and cultural development. INRS ranks first in Quebec in research intensity. It is made up of five interdisciplinary research and training centres located in Quebec City, Montreal, Laval, and Varennes, and Charlevoix, which focus their efforts on strategic sectors: water, earth, and environment (Eau Terre Environnement Research Centre); energy, materials, and telecommunications (Énergie Matériaux Télécommunications Research Centre); urbanization, culture, and society (Urbanisation Culture Société Research Centre); and health and biotechnology (Armand-Frappier Santé Biotechnologie Research Centre), and Ruralités durables (a center currently under development). Its community includes nearly 1,500 members, including students, postdoctoral fellows, faculty members, and staff. SOURCE Institut National de la recherche scientifique (INRS)

Innovative Molecules Offer Good News in the Fight Against HIV and Other Viral Infections Français
Innovative Molecules Offer Good News in the Fight Against HIV and Other Viral Infections Français

Cision Canada

time03-07-2025

  • Health
  • Cision Canada

Innovative Molecules Offer Good News in the Fight Against HIV and Other Viral Infections Français

INRS team is exploring the potential of saponins, a group of natural molecules found in many plants LAVAL, QC, July 3, 2025 /CNW/ - Innovative, nontoxic molecules developed by a research team at the Institut national de la recherche scientifique (INRS) could pave the way for new safe and effective antiviral therapies for prevention and treatment purposes. Are there natural compounds with antiviral properties, particularly against the human immunodeficiency virus (HIV) that causes AIDS? Betulinic acid has long been recognized in medical and scientific communities for its antiviral potential. This molecule, found in various plants, is especially abundant in the bark of white birch trees—a common byproduct of the forestry industry. However, the use of betulinic acid and some of its derivatives in medicine has been limited by a major drawback: the molecules are poorly soluble in water. This limits their absorption by the body and complicates their use in medicine. A discovery by INRS Professor Charles Gauthier 's team, part of the INRS-UQAC Joint Research Unit in Sustainable Health, could significantly unlock the potential of this molecule. Their findings * were recently published in Chemistry – A European Journal. Creating a Promising and Novel Molecule In their research, Professor Gauthier's team studied two natural molecules: betulinic acid and echinocystic acid. Both belong to a family of compounds known as triterpenes and share a similar chemical structure. The researchers chemically modified these molecules using a novel, controlled method by attaching a specific sugar called Lewis X. This sugar is structurally similar to those that define human blood groups. The modification resulted in new chimeric compounds known as "saponins." These saponins had never been described in scientific literature before. They offer several advantages for potential antiviral use: they are significantly more water-soluble than triterpenes, they dissolve well in biological environments, and unlike similar substances that can be toxic, they are safe for human cells and mice. Most importantly, they effectively block HIV activity. The team observed that saponins prevent the virus from using certain carbohydrate-specific proteins, known as Lewis-binding proteins, found on immune cells called DC-SIGN and L-SIGN, to spread to CD4+ cells, the main targets of HIV. "Our results show that these are among the most potent monovalent inhibitors ever identified for blocking this HIV transfer mechanism, even when used at very low concentrations," explains INRS Professor Gauthier, who specializes in chemistry of carbohydrates and natural products. He is also a member of the Pasteur Network. HIV, Ebola disease, dengue fever, coronaviruses: the potential is vast These chimeric molecules capable of blocking viral entry into immune cells—a critical step in infection—are a first of their kind. Saponins could serve as a foundation for developing broad-spectrum antiviral agents that block infection at the earliest stage, such as during sexual transmission of HIV. "While it's known that human breast milk contains oligosaccharides that protect infants from HIV infection during early breastfeeding, we are the first to demonstrate that saponins can inhibit HIV entry via DC-SIGN and L-SIGN receptors," says doctoral student in biology at INRS and lead author Oscar Javier Gamboa Marin. "Despite progress in this field, very few studies have focused on inhibiting DC-SIGN and L-SIGN using Lewis-type carbohydrates," he adds. Another promising feature of saponins is their ability to spontaneously form structures called micelles or to integrate into liposomes. This could further enhance their antiviral effectiveness, particularly through improved targeting of virus-infected cells, and holds out promising research potential. Moreover, since DC-SIGN and L-SIGN proteins are also exploited by other dangerous viruses such as Ebola, dengue, and SARS-CoV-2, saponins open new avenues for developing broad-spectrum antiviral agents against these diseases. About the studies* The article entitled Lewis-X-Containing Triterpenoid Saponins Inhibit DC-SIGN- and L-SIGN-Mediated Transfer of HIV-1 Infection was co-authored by Oscar Javier Gamboa Marin, Kurtis Ng, Nitish Verma, Assi Gérard Flavien Yapi, Ralph Pantophlet, and Charles Gauthier. The article entitled Immunological and Toxicological Assessment of Triterpenoid Saponins Bearing Lewis-X- and QS-21-Based Trisaccharides was co-authored by Oscar Javier Gamboa Marin, Yasmine Adda-Bouchard, Balla Sylla, Nitish Verma, Tania Charpentier, Maya Huber, Guillaume Lopez, André Pichette, Alain Lamarre, and Charles Gauthier. This work was made possible thanks to the support of the Natural Sciences and Engineering Research Council of Canada, the Fonds de recherche du Québec, the Armand-Frappier Foundation, and the Swine and Poultry Infectious Diseases Research Center. INRS is an academic institution dedicated exclusively to graduate research and training in strategic sectors in Quebec. Since 1969, as per its mission, it has actively contributed to Quebec's economic, social, and cultural development. INRS ranks first in Quebec in research intensity. It is made up of five interdisciplinary research and training centres located in Quebec City, Montreal, Laval, and Varennes, and Charlevoix, which focus their efforts on strategic sectors: water, earth, and environment (Eau Terre Environnement Research Centre); energy, materials, and telecommunications (Énergie Matériaux Télécommunications Research Centre); urbanization, culture, and society (Urbanisation Culture Société Research Centre); and health and biotechnology (Armand-Frappier Santé Biotechnologie Research Centre), and Ruralités Durables Research Centre (a center currently under development). Its community includes nearly 1,500 members, including students, postdoctoral fellows, faculty members, and staff.

New tool for cutting DNA: promising prospects for biotechnology
New tool for cutting DNA: promising prospects for biotechnology

Yahoo

time19-04-2025

  • Science
  • Yahoo

New tool for cutting DNA: promising prospects for biotechnology

MONTREAL, April 14, 2025 /CNW/ - An INRS team discovers a new family of enzymes capable of inducing targeted cuts in single-stranded DNA. A few years ago, the advent of technology known as CRISPR was a major breakthrough in the scientific world. Developed from a derivative of the immune system of bacteria, CRISPR enables double strands of nucleotides in deoxyribonucleic acid (DNA) to be cut. This makes it possible to specifically modify a targeted gene in plant, animal and human cells. Ultimately, CRISPR became a preferred method in the search for treatments for acquired or hereditary diseases. Recently, Professor Frédéric Veyrier at the Institut national de la recherche scientifique (INRS) and his team developed a new genetic tool based on a family of specific enzymes called Ssn that allows targeted cuts to be induced exclusively in single-stranded DNA. The results of their work were recently published in the journal Nature Communications. This major breakthrough sheds light on a crucial genetic mechanism that could revolutionize a multitude of biotechnology applications. A form of DNA with a key role Single-stranded DNA is less common than double-stranded DNA. It is often found in some viruses and plays a key role in certain biological processes, such as cell replication or repair. Single-stranded DNA is also used in many technologies (sequencing, gene editing, molecular diagnostics, nanotechnology). To date, no endonuclease – enzyme that cuts DNA – has been described as exclusively targeting a single-stranded DNA sequence, which has constituted a barrier to the development of technologies based on this type of DNA. Now, for the first time in a laboratory, Professor Veyrier's team has identified a family of enzymes capable of cutting a specific sequence in single-stranded DNA: the family of Ssn endonucleases. To achieve this, the research team at INRS's Armand-Frappier Santé Biotechnologie Research Centre first characterized a new family of endonucleases part of the GIY-YIG superfamily called Ssn. More specifically, researchers focused on one of these enzymes in the bacterium Neisseria meningitidis, also known as the meningococcus. The enzyme targeted in the study is crucial to the exchange and alteration of genetic material, which influences evolution. "In studying it, we found that it recognizes a specific sequence that is found in many instances in its genome and plays a key role in the natural transformation of the bacterium. This interaction directly influences the dynamics of the bacterial genome," explains Professor Veyrier, a specialist in genomic bacteriology and evolution. In addition to this fundamental discovery, INRS's research scientists identified thousands of other similar enzymes. "We demonstrated that they are able to recognize and specifically cut their own single-stranded DNA sequence. Thousands of enzymes therefore have this property with their own specificity," adds Alex Rivera-Millot, a postdoctoral fellow on Professor Veyrier's team and co-first author of the study. An undeniable asset for health research These results, which represent a new tool for DNA recognition and exchange, are significant. They pave the way to many novel applications in biology and medicine. On the one hand, understanding this mechanism could help better control the bacteria in question and the associated infections. On the other, the discovery of enzymes specific to single-stranded DNA makes it possible to develop more precise and efficient genetic manipulation tools. This could namely improve methods of gene editing, DNA detection and molecular diagnosis. These enzymes could also be used to detect and manipulate DNA in various medical and industrial applications, such as pathogen detection or genetic manipulation for medical and therapeutic purposes. All of these avenues hold significant promise for addressing many health issues. Currently, there is a patent pending for the results of this work. About the study Chenal, M.*, Rivera-Millot, A.*, Harrison, L.B. et al. Discovery of the widespread site-specific single-stranded nuclease family Ssn. Nat Commun 16, 2388 (2025). This work was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes of Health Research (CIHR) and the Fonds de recherche du Québec – Santé (FRQS). About INRS INRS is an academic institution dedicated exclusively to graduate research and training in strategic sectors in Quebec. For the past 55 years, it has actively contributed to Quebec's economic, social, and cultural development. INRS is first in Canada in research intensity. It is made up of four interdisciplinary research and training centres located in Quebec City, Montreal, Laval, and Varennes, which focus their efforts on strategic sectors: water, earth, and environment (Eau Terre Environnement Research Centre); energy, materials, and telecommunications (Énergie Matériaux Télécommunications Research Centre); urbanization, culture, and society (Urbanisation Culture Société Research Centre); and health and biotechnology (Armand-Frappier Santé Biotechnologie Research Centre). The INRS community includes over 1,500 students, postdoctoral fellows, and faculty and staff members. SOURCE Institut National de la recherche scientifique (INRS) View original content to download multimedia:

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