In the first quantitative, real-time imaging study of
the travels of the malaria parasite Plasmodium through
mammalian tissue, researchers at the Pasteur Institute in Paris
found the parasites 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 Ménard,
a Howard Hughes Medical Institute (HHMI) international research
scholar who led the study.
Ménard and colleagues report their findings in the February 2006
issue of the journal Nature Medicine, published online on
January 22, 2006.
When a mosquito infected with Plasmodium bites a
mammal, the immature 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 fluorescently tagged
Plasmodium parasites, and then allowed the mosquitoes 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 appeared 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
interacting with key mammalian immune cells, suggesting that the
immune cells were destroying them.
A small number of the parasites in the lymph nodes, however,
escaped degradation and began to develop into forms usually found
only in the liver. Up to now, researchers believed that, although
both blood and lymphatic vessels take up Plasmodium
parasites, 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 completely
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 responds to infection, he
noted.
Another unexpected finding adds even more complexity to the
mammalian 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 developing 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 response. 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 observed.
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.
Editor's Note: The original news release can be found here.