[afro-nets] Malaria parasites develop in lymph nodes

[Leela McCullough <leela@healthnet.org>]

Malaria Parasites Develop In Lymph Nodes
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http://www.medicalnewstoday.com/medicalnews.php?newsid=36450
23 Jan 2006

In the first quantitative, real-time imaging study of the trav-
els of the malaria parasite Plasmodium through mammalian tissue,
researchers at the Pasteur Institute in Paris found the para-
sites developing in an unexpected place: the lymph nodes.

The parasites' presence in the lymph nodes almost certainly has
implications for the mammalian immune response, said Robert Mé-
nard, a Howard Hughes Medical Institute (HHMI) international re-
search scholar who led the study.

Ménard and colleagues report their findings in the February is-
sue of the journal Nature Medicine, published online on January
22, 2006.

When a mosquito infected with Plasmodium bites a mammal, the im-
mature parasites travel to the animal's liver, which, until now,
scientists thought was the only place they could develop, Ménard
said. Once they have fully developed, the parasites burst out of
the liver cells and infect red blood cells, beginning the onset
of malaria.

Although researchers understand this life cycle, no one has
measured directly how many parasites a mosquito bite transmits
or where else in a mammal's body they travel, said Ménard. To
find out, he and his colleagues infected mosquitoes with fluo-
rescently tagged Plasmodium parasites, and then allowed the mos-
quitoes to bite a mouse. From each mosquito bite, they found an
average of 20 fluorescent parasites embedded in the animal's
skin. Ménard found that the parasites moved through the skin in
a random, circuitous path at a speed that is amongst the fastest
recorded for any migrating cell. After leaving the skin, the
parasites frequently invaded blood vessels. That was no surprise
to Ménard, since they need to travel through blood vessels to
get to the liver. However, many of the parasites also invaded
lymphatic vessels. About 25 percent of the parasites injected by
the mosquito bites were drained by lymphatic vessels and ended
up in lymph nodes close to the site of the bite. Their journey
seemed to stop there, as the malaria parasites almost never ap-
peared in lymph nodes farther away.

Within about four hours of the mosquito bite, many of the lymph-
node parasites appeared degraded. They were also seen interact-
ing with key mammalian immune cells, suggesting that the immune
cells were destroying them.

A small number of the parasites in the lymph nodes, however, es-
caped degradation and began to develop into forms usually found
only in the liver. Up to now, researchers believed that, al-
though both blood and lymphatic vessels take up Plasmodium para-
sites, they all end up in the liver, Ménard said. "Nobody had
proposed that they actually might stop" in the lymph nodes and
develop there, he observed.

By 52 hours after the mosquito bites, no parasites remained in
the lymph nodes, which suggests that they can't develop com-
pletely there, Ménard said. Only fully developed parasites can
infect red blood cells and cause malaria, so the lymph-node
parasites probably don't contribute to the appearance of malaria
symptoms, he added. But even partially developed or destroyed
parasites could significantly affect how the immune system re-
sponds to infection, he noted.

Another unexpected finding adds even more complexity to the mam-
malian immune response to the malaria parasite. An hour after a
mouse was bitten, nearly half of the parasites remained in the
animal's skin, and some were detected there even after seven
hours. "That's really surprising," Ménard said.

Although he cautions that those numbers may be specific to mice
and the species of Plasmodium the scientists used, it's likely
that at least some parasites remain in the skin of any mammal
bitten by a malarial mosquito until immune cells come along to
sweep them out, Ménard said. This second influx of parasites
could prompt a somewhat different immune response in the host,
and those parasites might have different fates. Parasites devel-
oping in the lymph nodes could have two opposite effects on the
body's immune response, he explained. They might alert the body
that an invader is present and activate a protective immune re-
sponse. On the other hand, their presence in the lymph nodes
might desensitize the body to the parasites, blunting the immune
system's response to liver and blood-cell infection.

"We have to integrate all these new data into something that
makes sense from the immune standpoint," the researcher ob-
served. Understanding the intricacies of the mammalian immune
response to Plasmodium infection might help scientists create
better vaccines, including vaccines that target parasites before
they develop in the liver, Ménard said. Parasite development in
lymph nodes could even be one reason there is so much tolerance
to these parasites, he suggested.

Jennifer Donovan
Howard Hughes Medical Institute
mailto:donovanj@hhmi.org
http://www.hhmi.org


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Leela McCullough, Ed.D.
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