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 – a scientist at the Research Institute of the McGill University Health Centre (RI-MUHC) and McGill University. 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 – white blood cells – 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 – and potentially fatal – visceral form.
The researchers discovered that a metalloprotease – a molecule called GP63 – found on the surface of the parasite, plays a role in neutralizing the macrophage’s defences. “Our results demonstrate the mechanism through which the GP63 protease alters the function of the macrophages by activating its own negative regulatory mechanisms,” says Dr. Olivier. “The infected cells act ‘frozen’, which hinders the body’s innate inflammatory immune response and leads to infection.”
The work is significant in that it is the first study that explains how the leishmania parasite blocks the immune function of macrophages. “Our research indicates that the GP63 protease is the target of choice for innovative future treatments, in terms of prevention,” says Dr. Olivier.
The GP63 protease directly activates other key molecules that negatively regulate the function of the host cell. “Better 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,” 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 McGill University’s Faculty of Medicine.
This study was funded by a grant from the Canadian Institutes of Health Research (CIHR).
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, McGill University’s Faculty of Medicine, Dr. Maxime Hallé, Dr. Michel L.Tremblay, Department of Biochemistry, McGill University, Dr. Robert W. McMaster, Department of Medical Genetics, University of British Columbia, Vancouver Hospital.
The Research Institute of the McGill University 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 McGill 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.
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