2023-07-30 07:00:54
Professor Simona Stäger’s team from the National Institute for Scientific Research (INRS) made a discovery while studying the human immunodeficiency virus (HIV).
Researchers have identified the mechanism by which memory CD4 T cells – a type of cell with a major role in the immune response in humans – are predisposed to cell death in people living with HIV.
Professor Stäger and her team started from work published in Cell Reports in 2018. These had been carried out on mouse cells infected with the parasite Leishmania donovani. It described how a chronic inflammatory environment predisposes certain cells to cell death, also called “apoptosis”.
This premise encouraged them to think that such a mechanism could be found in other chronic infectious diseases, such as HIV.
“This is an important finding, since this cell death mechanism that we have demonstrated could have implications in other types of chronic infections such as COVID-19 or visceral leishmaniasis in humans,” notes Professor Stäger by press release.
Molecular fingerprint
In most people living with HIV and receiving antiretroviral therapy, residual inflammation persists despite some control of the viral load by this therapy. The memory CD4 T cells of these people undergoing treatment are known to be prone to apoptosis.
Until now, however, this mechanism remained largely unknown.
The researchers found that CD4 memory T cells have higher expression of the TLR7 receptor and the IRF5 transcription factor, which imprints on these cells – and predisposes them to cell death. The results also demonstrate that IRF-5 inhibitory peptides can block this predisposition.
The imprint observed is the consequence of a chronic inflammatory environment. The results could therefore have implications for other infectious diseases of the same type.
Memory cells
A memory cell allows the immune system to better protect itself against a pathogen after a first encounter with it. This is the basic principle of vaccines, which provoke a memory immune response and thus induce immunity against the infectious agent. The loss of these memory cells therefore represents a major risk for anyone suffering from a chronic infection.
Thus, in 80% of people living with HIV and receiving treatment, this discovery would strengthen the protection of memory cells. For the 20% of individuals for whom the treatment remains ineffective, the breakthrough proposed by Professor Stäger’s team could potentially open the door to a more appropriate therapy.
It should be noted that the project was led head-on by INRS doctoral student Liseth Carmona Perez.
His research interest focuses on infectious diseases and T lymphocytes, cells that play a major role in the immune response in humans. Liseth worked under the supervision of Professor Stäger, and was accompanied by three other students, her colleagues Linh Thuy Mai, Tanja Stögerer and Sharada Swaminathan, at the Center Armand-Frappier Santé Biotechnologie in Laval.
As part of this publication of the results in the journal JCI Insight, Professor Stäger and doctoral student Carmona-Perez collaborated with the laboratory of Dr. Betsy Barnes at the Feinstein Institute for Medical Research in New York.
They also worked with HIV specialists, namely Doctor Jean-Pierre Routy of McGill University and his postdoctoral fellow Stéphane Isnard, as well as Julien van Grevenynghe, professor at INRS, and Xavier Dagenais Lussier, doctoral student at the INRS at the time of the study. (N.P.)
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