New discovery points the way towards malaria “vaccine”
MUHC/McGill study opens the door to malaria-prevention therapies
Malaria kills anywhere from one to three million people around
the world annually and affects the lives of up to 500 million more.
Yet until now, scientists did not fully understand exactly how the
process that caused the disease’s severe hallmark fevers
began.
A team led by Dr. Martin Olivier from the Research Institute of the
McGill University Health Centre (RI-MUHC) and McGill University in
Montreal has solved this mystery, and may have blazed a trail
towards the development of vaccine-like treatments to limit the
severity of the devastating parasitic ailment. . The results of
their study will be published August 21 in the journal PLoS
Pathogens.
Malaria is a mosquito-borne infectious disease spread by parasites
from the Plasmodium family. Inside the human body, the malaria
parasite infects red blood cells where it survives and reproduces
by feeding on the cells’ contents. Eventually the cells burst,
releasing the parasites and also a waste byproduct of their
reproductive process: hemozoin.
Researchers at the RI-MUHC and McGill University, discovered that
hemozoin, a crystal-like substance may be the missing link that
explains why malaria leads to devastating inflammation and
fever.
“Our results describe the mechanism by which the hemozoin activates
the immune system, resulting in the production of inflammation
mediators and in the high fever that we witness in malaria
patients,” said study first-author Dr. Marina Tiemi Shio of the
RI-MUHC.
Hemozoin is first ingested by ‘cleaning’ cells called macrophages,
explained the researcher which leads to a chain reaction ending in
the activation of the inflammasome: an important structure inside
immune cells which lead to inflammation. Activation of the
inflammasome produces the body’s fever mediator, interleukin beta
(IL-beta).
“Our work is a milestone in that it is the first study that reveals
the enzymes that act as intermediary between the hemozoin and
inflammasome,” explained Dr. Olivier. “Now our picture of the
process that goes from infection to fever is more or less
complete.”
“On the other hand we also proved that malaria is too complex to be
narrowed down to one single mechanism,” he continued. “In the
absence of either IL-beta or a functional inflammsaome, the
development of the disease is delayed but not completely stopped.
Although the discovery of this relationship is important, there are
other mechanisms at work.”
The mechanisms that go from the activation of the inflammasome to
the onset of the malaria symptoms were already familiar to
scientists, but until now the beginning of the process was unknown.
“These results prove the primary role hemozoin plays in the
development of malaria, and designates it as a favoured choice for
future innovative treatments,” added Dr. Olivier.
The researchers believe it will be possible to familiarize the
immune system to small quantities of hemozoin and diminish the
inflammatory response in the event of infection, according to a
principle similar to that of vaccines.
Dr. Martin Olivier is a researcher in the Infection and Immunity
Axis of the Research Institute of the McGill University Health
Centre. He is also Associate Professor at McGill University’s
Faculty of Medicine.
Dr Marina Tiemi Shio
Dr Marina Tiemi Shio is a post-doctoral trainee with Dr Olivier,
working in the Infection and Immunity Axis of the Research
Institute of the McGill University Health Centre.
Funding
This study was funded by a grant from the Canadian Institutes of
Health Research (CIHR).
Partners
This article was co-authored by Dr. Marina Tiemi Sho, Dr. Myriam
Savaria, Dr. Marie-Josée Bellemare, from the Research Institute of
the McGill University Health Centre and McGill University, Dr. D.
Scott Bohle from McGill University and Dr. Martin Olivier from the
RI MUHC and McGill University and, by Dr. Stephanie C. Eisenbarth,
and Dr. Richard A. Flavell from Yale University, by Dr. Adrien F.
Vinet and Dr. Albert Descoteaux of the l’Institut Armand-Frappier,
by Dr. Kenneth W. Harder of the University of British Columbia, and
by Dr. Fayyaz S. Sutterwala from the University of Iowa.
Once the embargo is lifted you will find this press release, with
the original article and a short audio interview by following this
link:
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