New discovery could lead to treatment for visceral leishmaniasis

A discovery by Simona Stäger’s team could help find a treatment for the most severe form of leishmaniasis.

Leishmaniasis is a tropical disease that affects a growing number of people around the world. Between 700,000 and 1 million new cases are reported each year. Caused by a protozoan parasite of the genus Leishmania, which is transmitted to humans by the simple bite of a sand fly, leishmaniasis comprises three clinical forms, of which the visceral form is the most serious. If left untreated, visceral leishmaniasis, also known as black fever, is almost always fatal. Most cases occur in Bangladesh, Brazil, Ethiopia, India, Nepal and Sudan.

Professor Simona Stäger from the National Institute for Scientific Research (INRS) and her team, in collaboration with other researchers from INRS and McGill University, have observed a surprising immunological mechanism related to chronic visceral leishmaniasis. This discovery could be an important step towards a new therapeutic approach for this disease. The results of her research have been published in the journal Cell Reports.

In many infections, CD4 T cells play a key role in the defense of the affected organism. Unfortunately, in the case of chronic infections such as leishmaniasis, maintaining the number of functional CD4 cells becomes an important issue, since the immune system is constantly activated to react against the pathogen that affects the infected person.

New immunity soldiers to the rescue

However, the study carried out by Professor Stäger in her laboratory at the INRS Armand-Frappier Santé Biotechnology Research Center suggests that these cells may have more than one trick up their sleeve to maintain their vitality.

We have discovered a new population of CD4 cells in mice infected with the parasite responsible for visceral leishmaniasis. “These T cells have interesting properties.”


Simona Stäger, expert in immunology of infectious diseases

By observing these new cells, the scientists verified that they increase in number during the chronic phase of the disease and also that, like the progenitor cells, they are capable of self-renewal or differentiation into other effector cells responsible for eliminating the parasite, or regulatory cells. . cells that inhibit the host response.

Professor Simona Stäger points out that CD4 T cells normally differentiate from “naïve” CD4 T cells into effector cells. But during chronic infections, due to the constant need to generate effector cells, naïve CD4 T cells are in high demand and can become depleted.

“We believe that in the chronic phase of visceral leishmaniasis, the new population that we have identified is responsible for generating effector and regulatory cells. This would allow the host to avoid depletion of its existing pool of naïve CD4 T cells for a given antigen,” he explains. Doctor. student and first author of the study, Sharada Swaminathan.

The new population of lymphocytes discovered by the INRS team could be a decisive immune booster, replacing the over-sought naïve CD4 T cells.

“If we can figure out how to direct this new population of lymphocytes to differentiate into a protective effector cell, it could help the host get rid of the Leishmania parasite.” -; Simona Stäger, deputy director of Infectiopole and member of the Pasteur Network

A cure for other infections?

The study also mentions that cells similar to this new population of CD4 T lymphocytes have been observed in mice infected with the lymphocytic choriomeningitis virus and in mice carrying the intestinal worm H. polygyrus. Therefore, it is very possible that this population is present in other chronic infections or in other chronic inflammatory environments.

This overlap sets the stage for an even broader scope for the discovery made by Professor Stäger’s team. “If our hypothesis is correct, these cells could be used therapeutically not only for visceral leishmaniasis, but also for other chronic infections,” concludes the researcher.

Fountain:

National Institute of Scientific Research – INRS

Magazine reference:

Swaminathan, S., et al. (2024). CD4 T cells expressing LAG-3 and CXCR5 display progenitor-like properties during chronic visceral leishmaniasis. Cellular reports. doi.org/10.1016/j.celrep.2024.113879.