~tasha~
Age: 124
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Researchers in Trinity College Dublin and Oxford University have made
an important breakthrough in malaria.
In a paper published in the world's number one genetics journal,
Nature Genetics, they describe how an important immune system protein
called Mal plays a major role in determining whether individuals
become infected with and ultimately succumb to malaria. They also show
that Mal has a protective role against TB and pneumonia, and possibly
many different infections. These insights represent a major advance in
our understanding of how the immune system works during infection and
indicate possible new therapies to use in the treatment of malaria and
other infectious diseases. The work was carried out by a team at
Oxford led by Adrian Hill, Professor of Human Genetics, University of
Oxford, funded by the Wellcome Trust, and a team at Trinity led by
Luke O'Neill, Professor of Molecular Immunology and Head of the School
of Biochemistry and Immunology, Trinity College Dublin, funded by
Science Foundation Ireland.
Mal was originally discovered in O'Neill's laboratory in 2001. 'We
knew we had found an important part of the immune system, but this
recent discovery clearly identifies Mal as being important for our
immune system's capacity to fight infections such as malaria' says
Prof O'Neill. Mal is in effect an alarm system for the immune system.
When the body is infected with the malaria parasite or other germs, a
set of sensors called Toll-like receptors (TLRs) lock onto the
intruder. TLRs relay the detection via Mal, which wakes up the immune
system to mobilise and defend us. The Oxford group discovered that Mal
comes in 2 types in humans. One of the types turns out to be just
right for the immune system to work normally, whereas the other type
actually results in too strong a stimulation. If you have the
overactive type, you are twice as likely to succumb to infection
because your immune system goes into over-drive and disease results,
in a manner akin to 'friendly fire'. "Our work provides a striking
example of how a key molecule in our immune system can be sacrificed
to give some people better resistance to infectious disease." says
Prof Hill
Over 6000 patients with malaria, TB or pneumonia were studied, in the
Gambia, Vietnam, Turkey and the UK. Having the overactive Mal doubled
the risk of disease, with a 4 times greater risk of severe malaria in
some populations. The work suggests that drugs that target the Mal
pathway might be very useful in the treatment of malaria and TB. . 'We
are very excited by the prospect that our work might be useful in the
effort to come up with new strategies to prevent death during these
infections' says O'Neill. Malaria and TB account for over 5 millions
deaths per year in the developing world, particularly in children.
"This works provide key evidence that modulating this pathway in
humans could lead to better resistance against many important
infectious diseases." says Hill.
