Obviously malaria is able to hide
from the immune system and this work is beginning the task of stripping that
protection away. Any pathway that opens
the parasite to an attack by the immune system will take us a long way down the
road toward a cure.
Yet this work appears to be just
a good beginning and we are a long ways away from useful tools.
Importantly, the disease is now
coming under a spirited attack with perhaps some sense that we can see this
thing off once and for all.
Unveiling malaria's cloak of invisibility
by Staff Writers
The discovery by researchers from the Walter and Eliza Hall
Institute of a molecule that is key to malaria's 'invisibility cloak' will help
to better understand how the parasite causes disease and escapes from the
defenses mounted by the immune system.
The research team, led by Professor Alan Cowman from the
institute's Infection and
Immunity division, has identified one of the crucial molecules that
instructs the parasite to employ its invisibility cloak to hide from the immune
system, and helps its offspring to remember how to 'make' the cloak.
In research published in the journal Cell Host and Microbe, Professor
Cowman and colleagues reveal details about the first molecule found to control
the genetic expression of PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1),
a protein that is known to be a major cause of disease during malaria
infection.
"The molecule that we discovered, named PfSET10, plays an
important role in the genetic control of PfEMP1; an essential parasite protein
that is used during specific stages of parasite development for its
survival," Professor Cowman said.
"This is the first protein that has been found at what we call the
'active' site, where control of the genes that produce PfEMP1 occurs. Knowing
the genes involved in the production of PfEMP1 is key to understanding how this
parasite escapes the defenses deployed against it by our immunesystem,"
he said.
PfEMP1 plays two important roles in malaria infection. It enables the
parasite to stick to cells on the internal lining of blood vessels, which
prevents the infected cells from being eliminated from the body.
It is also responsible for helping the parasite to escape destruction
by the immune system, by varying the genetic code of the PfEMP1 protein so that
at least some of the parasites will evade detection.
This variation lends the parasite the 'cloak of invisibility' which
makes it difficult for the immune system to detect parasite-infected cells, and
is part of the reason a vaccine has remained elusive.
Professor Cowman said identification of the PfSET10 molecule was the
first step towards unveiling the way in which the parasite uses PfEMP1 as an
invisibility cloak to hide itself from the immune system.
"As we better understand the systems that
control how the PfEMP1 protein is encoded and produced by the parasite,
including the molecules that are involved in controlling the process, we will
be able to produce targeted treatments that would be more effective in
preventing malaria infection in the approximately 3 billion people who are at
risk of contracting malaria worldwide," he said.
Each year more than 250 million people are infected with malaria and
approximately 655,000 people, mostly children, die. Professor Cowman has spent
more than 30 years studying Plasmodium falciparum, the most lethal of the four
Plasmodium species, with the aim of developing new vaccines and treatments for
the disease.
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