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Archive for Friday, April 24, 2009

Immune cell offers new clue to worst malaria cases

April 24, 2009

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— A novel immune cell may offer an important new clue to why malaria kills some people and not others.

Australian researchers discovered a specialized cell crowding the bloodstream of severe malaria sufferers but not the less sick — a cell that seems to switch off a different immune-system attack.

Now the question: Is that cell responsible for worsening malaria, or a consequence of having a severe case?

The research, by Monash University immunologists in Australia, is reported today in the journal PLoS Pathogens, published by the Public Library of Science.

The World Health Organization estimates that nearly a quarter-billion people get malaria each year, and it kills almost 1 million, the vast majority of them young children. Many drugs have lost their effectiveness against the parasite and there is no vaccine, although advanced testing of an experimental candidate that promises partial protection is under way.

Scientists hunting better protections are focusing on a big mystery: Why people who initially are equally healthy and become infected in the same village can have such radically different outcomes. The answer isn’t just how many of the mosquito-spread parasites they harbor. In parts of Mali, in western Africa, researchers have measured huge numbers of malaria parasites in children able to play soccer, only a fraction of whom eventually become very ill, said Dr. Rick Fairhurst of the U.S. National Institutes of Health.

The major clue until now: People with gene mutations that can cause sickle cell disease or similar blood disorders also have some protection against severe malaria. NIH scientists have evidence linking malaria deaths to a cycle of out-of-control inflammation, triggered by how strongly the parasites bind to various cells in the bloodstream, something those gene mutations limit.

Today’s report brings another clue.

The immune system harbors numerous types of cells that have different jobs. So-called regulatory T cells, or T-regs, are thought to help keep the system in balance by tamping down overactive immune responses from other cells.

Monash University researchers tested 33 malaria-infected adults in Papua, Indonesia, half of whom were severely ill.

Both sets of patients harbored similar numbers of T-regs. But in the severe patients, many of those cells had changed to become extra-suppressive, thanks to a new and distinct receptor that formed on the cells’ surface, reported immunologist Magdalena Plebanski, the lead researcher.

Also, the severe patients harbored more parasites — and different immune cells designed to eliminate those parasites were less active, the researchers found.

“Our results indicate that severe malaria is accompanied by the induction of highly suppressive T-reg cells that can promote parasite growth,” Plebanski concluded. She urged that vaccine studies carefully examine whether recipients form this type of immune reaction.

NIH researchers plan to do that. But this study cannot tell whether the immune-suppressing cells triggered worse malaria, NIH’s Fairhurst cautioned. It’s possible that they formed as the body sought to lower that out-of-control inflammation.

But if they’re key players, then people with sickle-cell trait or other known protective gene mutations also should harbor fewer of the suppressive cells, he noted.

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