Innate Immune Memory in Mosquitoes: The Latest Buzz in the Fight against Malaria

Research on Malaria, World Health Organisation/Institut Pasteur. Female mosquito with body swollen with blood of person she has bitten. It is at this stage that the Malaria parasite is passed to the victim.

For many of us mosquitoes are an itchy aggravation. They come in the evenings in the warmer months. They disrupt hikes, camping trips and picnics, leaving behind itching reminders that have us reaching for antihistamines and no-itch creams. For people in some areas of the world however, mosquitoes are more than just a pest with an itchy calling card, they are a deadly menace. Mosquitoes of the genus Anopheles can carry Plasmodium, the parasitic micro-organism that causes malaria.

According to the World Health Organization, there were an estimated 243 million cases of malaria worldwide in 2008. Most of these cases were in Africa, followed by South-East Asia and the Eastern Mediterranean (1). In that year, malaria caused an estimated 863,000 deaths, and tragically, the majority of these deaths were in children younger than five.

PLASMODIUM VIVAX LIFE CYCLE, A)ANOPHELES MOSQUITO BITES MAN, SPOROZOITES FROM SALIVARY GLANDS GET INTO THE BLOOD. B)SCHIZONTS DEVELOP IN LIVER. C)MEROZOITES BREAK LOOSE AND ENTER RED BLOOD CELLS (RBC). D)TRO- PHOZOITES DEVELOP INTO SCHIZONTS IN RBC'S. E)MEROZOITES BREAK OUT AND RE-INFECT RBC. F)MALE AND FEMALE GAMETO- CYTES DEVELOP IN RBC. G)MOSQUITO INGESTS GAMETOPHYTES, THEY FORM ZYGOTES ON CONTACT. H)OOCYSTS DEVELOP, GROW OUT OF STOMACH WALL OF MOSQUITO. I)OOCYSTS RUPTURE. PLASMODIUM VIVAX LIFE CYCLE

Considering these numbers, it is small comfort to know that mosquitoes fall victim to the Plasmodium parasite just like people do. But not all mosquitoes succumb; some manage to fight off the infection. But how do they do it? Insects do not have adaptive immunity, meaning they are unable to establish an immunological memory. Instead they rely on an innate immune system, which is believed to be hard-wired and unchangeable; in other words it can’t adapt to specific pathogenic infections. At the same time, we know that some invertebrates like insects can exhibit a memory-like response to pathogens. This response is called immune priming, and mosquitoes use it when they fight off Plasmodium infection. A team of researchers from the National Institute of Allergy and Infectious Diseases set out to find out how mosquitoes develop this response. The results of their study are published in the September 10 issue of Science (2).

The researchers infected two groups of mosquitoes by feeding them with blood filled with Plasmodium. One group was allowed to become infected; the other was placed in conditions that were too hot for the Plasmodium to grow. A week later, the mosquitoes from both groups were feed on the Plasmodium infested blood again. What the researchers found was that the group of mosquitoes who had been infected previously were much better at fighting off the infection the second time.

How did the previously-infected mosquitoes fight off the second infection? Well it turns out that mosquitoes have two weapons to use against parasitic infection. One weapon is the immune cells called granulocytes. Granulocytes can kill foreign bodies they detect in mosquitoes blood or signal another cell to come do it. When the researchers looked at their two groups of mosquitoes, they found that the previously infected mosquitoes had three times as many granulocytes as did the uninfected group.

The increased number of granulocytes might explain how the previously infected group of mosquitoes were better able to fight the second infection, but how did they come to have more of these infection-fighting cells? The answer to that question was bacteria. When Plasmodium infects a mosquito, it weakens the walls of the mosquito’s gut and allows the gut bacteria to enter parts of the body where they usually do not exist. This most likely triggers some antibacterial response that results in an increase in granulocyte cell numbers. When the researchers repeated their experiment after first treating the mosquitoes with antibiotics to eliminate their gut bacteria before the first feeding, they found no increase in granulocyte count. When there was no gut bacteria to be release by the Plasmodium infection there was no increase in immunity, and just as many insects died in the preinfected group as the control group.

mosquitoes

Finally, the researchers tried “vaccinating” mosquitoes using serum from mosquitoes who had been exposed to Plasmodium. Before they vaccinated the test group, they removed the granulocytes from the serum. When this test group was exposed to Plasmodium, they had less intense infections and got them 40% less often. Their conclusion? Something in the exposed mosquito blood cause an increase in granulocyte production.

Now if you are like me, you aren’t loosing any sleep over the fact that mosquitoes are falling victim to same parasite they spread to humans, but imagine if we could inoculate mosquito populations against Plasmodium infection. Sure, the mosquito population might increase by 40%, but that seems like a small price to pay for 863,000 lives.

References

  1. Malaria Causes and Deaths. World Health Organization Web site, accessed September 23, 2010. http://www.who.int/gho/mdg/diseases/malaria/situation_trends_mortality/en/index.html
  2. ResearchBlogging.org

  3. Rodrigues J, Brayner FA, Alves LC, Dixit R, & Barillas-Mury C (2010). Hemocyte differentiation mediates innate immune memory in Anopheles gambiae mosquitoes. Science (New York, N.Y.), 329 (5997), 1353-5 PMID: 20829487
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Kelly Grooms

Scientific Communications Specialist at Promega Corporation
Kelly earned her B.S. in Genetics from Iowa State University in Ames, IA. Prior to coming to Promega, she worked for biotech companies in San Diego and Madison. Kelly lives just outside Madison with her husband, son and daughter. Kelly collects hobbies including jewelry artistry, reading, writing, photography and knitting. She would like to be an avid runner, as evidenced by her growing collection of running gear and her single half-marathon finishers t-shirt.

3 thoughts on “Innate Immune Memory in Mosquitoes: The Latest Buzz in the Fight against Malaria

  1. “…but imagine if we could inoculate mosquito populations against Plasmodium infection. Sure, the mosquito population might increase by 40%, but that seems like a small price to pay for 863,000 lives.”

    The inoculation would not change the fact that these creatures have the infection crawling throughout them, in their stomachs and on their mouthparts, while they are fighting the infection. Inoculation (if it were possible) would make the mosquitoes able, inevitably, to resist, and would increase their numbers dramatically.

    In short, all this together would make them more able than ever to transmit the parasite. This research is flawed in loagical basis. Any child with two brain cells to rub together would tell you that the exact opposite of this approach would be the way to go. If we could find a way of removing or seriously damaging their immune system response against plasmodium then hopefully the pest would kill them before they had a chance to transmit it.

    Regards,

    James

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