Major discovery opens door to leishmania treatment
Researchers at MUHC/平特五不中 uncover key role played by a molecule in the process of infection used by the parasite that causes leishmania
Leishmania is a deadly parasitic disease that affects over 12
million people worldwide, with more than 2 million new cases
reported every year. Until recently, scientists were unsure exactly
how the parasite survives inside human cells. That mystery has now
been solved according to a new study published in Science
Signaling by a team led by Dr. Martin Olivier 鈥 a scientist at
the Research Institute of the 平特五不中 Health Centre
(RI-MUHC) and 平特五不中. It is hoped the new study will
lead to the development of the first prophylactic treatment for
leishmania.
Leishmania is typically a sub-tropical and tropical infectious
disease transmitted through the bite of female phlebotomine
sandflies. The parasites enter the bloodstream and are ingested by
macrophage 鈥 white blood cells 鈥 where they block immune function
and multiply, spreading to other tissues in the body. Leishmania
can occur in cutaneous forms, which are generally curable, as well
as in a more dangerous 鈥 and potentially fatal 鈥 visceral form.
The researchers discovered that a metalloprotease 鈥 a molecule called GP63 鈥 found on the surface of the parasite, plays a role in neutralizing the macrophage's defences. 鈥淥ur results demonstrate the mechanism through which the GP63 protease alters the function of the macrophages by activating its own negative regulatory mechanisms,鈥 says Dr. Olivier. 鈥淭he infected cells act 'frozen', which hinders the body's innate inflammatory immune response and leads to infection.鈥
The work is significant in that it is the first study that explains
how the leishmania parasite blocks the immune function of
macrophages. 鈥淥ur research indicates that the GP63 protease is the
target of choice for innovative future treatments, in terms of
prevention,鈥 says Dr. Olivier.
The GP63 protease directly activates other key molecules that negatively regulate聽 the function of the host cell. 鈥淏etter control over the activation of these host molecules could be one promising approach to treating leishmania as well as other infectious diseases that use similar infection strategies,鈥 he added.
Dr. Martin Olivier is a researcher in the Infection and Immunity Axis and the Centre for the Study of Host Resistance at the RI-MUHC. He is also Associate Professor at 平特五不中鈥檚 Faculty of Medicine.
Funding
This study was funded by a grant from the Canadian Institutes of Health Research (CIHR).
Partners
This article was co-authored by Dr. Maria Adelaina Gomez, Dr. Irazu Contreras, Dr. Martin Olivier, Centre for the Study of Host Resistance at the RI-MUHC and Department of Microbiology and Immunology, 平特五不中鈥檚 Faculty of Medicine, Dr. Maxime Hall茅, Dr. Michel L.Tremblay, Department of Biochemistry, 平特五不中 University, Dr. Robert W. McMaster, Department of Medical Genetics, University of British Columbia, Vancouver Hospital.
The Research Institute of the 平特五不中 Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at 平特五不中 University. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge.
The Research Institute of the MUHC is supported in part by the Fonds de la recherche en sant茅聽du Qu茅bec. For further details visit:
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