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How Mosquitoes Fight Malaria

Consider it poetic justice. Mosquitoes succumb to the parasite that causes malaria just like people do. But many are able to fight off the infection. Now researchers have figured out how the insect's immune system conquers the parasite—knowledge that could be used to combat the spread of malaria in humans.

An insect's immune system doesn't work like ours. It's not designed to adapt to specific threats over time, though it can still learn to fight off infections. This is evinced by the fact that many mosquitoes are able to fight off Plasmodium, the single-celled microbe that causes malaria. But researchers don't know exactly how insects do this.

To find out, vector biologist Janneth Rodrigues and colleagues at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, fed two groups of mosquitoes mouse blood crawling with Plasmodium. One group became infected, but the other—placed in a room too hot for Plasmodium to grow—did not. Seven days later, the researchers fed both groups the Plasmodium-infected mouse blood again. The infected group was up to 10 times better at killing the Plasmodium.

The mosquito appears to have two weapons in its arsenal. One is granulocytes. The team found three times as many of these immune cells in the preinfected group than they did in the uninfected group. When granulocytes detect a foreign body in a mosquito's blood, they can either kill it themselves or signal another cell to come do the job.

But granulocytes don't show up to save the day without help, says Rodrigues. Her team suspected that bacteria are also involved in the anti-Plasmodium response because the parasite weakens the walls of the mosquito's gut, and gut bacteria pour into parts of the body that they're not usually found in. That likely triggers more "baby immune cells" to start turning into granulocytes, says vector biologist and co-author Carolina Barillas-Mury, priming the immune system to battle the Plasmodium invaders.

To test whether this was the case, the team repeated the experiment but gave the mosquitoes antibiotics that deplete their gut bacteria. This time, the preinfected group did not increase its granulocyte count—and just as many of its members died as did those in the control group. "Preventing the malaria is probably actually an indirect effect of the system preventing the bacteria being in the wrong place," Barillas-Mury says.

To see if they could create a sort of malaria vaccine for mosquitoes, the researchers injected some of the insects with the serum of mosquitoes exposed to Plasmodium, but they removed the granulocytes from the serum. The mosquitoes that received the serum had less-intense Plasmodium infections and got them 40% less frequently when they were fed malaria-infected mouse blood, the team reports in the 10 September issue of Science. This shows that there is a factor in exposed mosquito blood that ramps up the production of granulocytes, says Barillas-Mury. If researchers could mimic that factor and place it in mosquito nets or spray it on the insects, they could immunize the bugs against infection and make them bad vectors for malaria, she says.

Vector biologist Marcelo Jacobs-Lorena of John Hopkins University in Baltimore, Maryland, agrees that understanding the biology of the mosquitoes' resistance could have practical applications. "Since the mosquito is an essential link for transmission to occur, this is important if we want to eliminate malaria from the mosquito."

This article has been corrected to better reflect nuanced differences between the insect and the human immune system. Also, a sentence regarding the mortality and reproduction of the infected mosquitoes has been removed because the information came from other studies.