A Mosquito's Immune System May Hold the Key to Malaria

The Anopheles gambiae mosquito acts as a major vector for the transmission of malaria in sub-Saharan Africa, carrying infected blood among people. Malaria killed nearly half a million humans around the globe in 2015, according to the most recent available numbers from the World Health Organization, but the disease rarely kills the mosquito that spreads it from person to person.

In a study published in Science Immunology on January 20, Julio Cesar Castillo, Ana Beatriz Barletta Ferreira, Nathanie Trisnadi, and Carolina Barillas-Mury, scientists at the National Institutes of Health, say they’ve figured out why this malaria-transmitting mosquito doesn’t succumb to the disease. The mosquito lacks the blood cells that humans possess. This, in conjunction with the mosquito’s immune response, means that Plasmodium, a malaria parasite, dies off without infecting it. The researchers hope to use their findings to investigate the ways such parasites thwart insects’ immune systems in the hopes of developing better transmission-blocking vaccines.

“What makes people really sick is that, after parasites invade the liver, they come out into the blood and then they can infect all our red blood cells,” says Carolina Barillas-Mury in a press-release interview. The malaria parasites also damage blood vessels’ surfaces by sticking to them, says Barillas-Mury. But since the mosquito doesn’t have red blood cells or blood vessels like humans do, Plasmodium can’t infect it. “This is a dead end,” says Barillas-Mury. So when malaria parasites find themselves in a mosquito, in order to survive they must escape through the mosquito’s salivary glands and travel to a new host.

In addition to its fortunate lack of red blood cells, the mosquito also possesses a unique immune response to Plasmodium. When the lining of the mosquito’s midgut comes into contact with the malaria parasite, it undergoes a nitration response. This triggers the release of hemocyte-derived microvesicles. These cells, which Barillas-Mury calls “sentinel cells,” help activate the mosquito’s complement-like system that limits Plasmodium infection.

So what does this mean for humans? Barillas-Mury says this immune response in the mosquito suggests that humans may have a similar response. Since many chronic inflammatory diseases are mediated by activation of complements like that displayed by the mosquito, says Barillas-Mury, better understanding how this immune response is triggered will help prevent the activation that causes people to suffer from conditions like rheumatoid arthritis or atherosclerosis.

Here’s the twist: Some varieties of Plasmodium can hide from the mosquito’s immune system, passing through its gut safely without triggering a response. So Barillas-Mury hopes she and her colleagues can recruit the mosquito’s immune system to make the parasite visible, destroying the disease in what’s known as a transmission-blocking vaccine. A transmission-blocking vaccine wouldn’t work perfectly on its own, but it could be a good complement to existing treatments.

There are already a handful of malaria drugs on the market, including preventative ones such as Malarone and post-exposure ones like Daraprim. In spite of this, people in developing nations are disproportionately affected by malaria, so developing new drugs and enhancing access to them continues to be a growing concern. Additionally, as the global climate warms, pathogens will spread beyond their current boundaries, affecting more and more people around the world. And while research funded by the NIH and other groups can’t single-handedly solve global health problems, this new research could contribute to the fight against preventable deaths worldwide.