Nav: Home

How malaria fools our immune system

January 14, 2016

Okinawa Institute of Science and Technology Graduate University (OIST) reconstructed the 3D structure of one of the proteins of Plasmodium falciparum, the causative agent of malaria and the antibodies that act as the first line of defense against the parasite. This research, published in Cell Reports, was conducted at the Structural Cellular Biology Unit, led by Prof. Ulf Skoglund. This study provides valuable knowledge for the design of anti-malaria drugs.

Plasmodium falciparum is transmitted to humans by the bite of some species of the Anopheles mosquito. Once inside the human body, the parasite soon reaches the liver where it matures and it is then ready to infect red blood cells, also called erythrocytes. The parasite survives by bursting from infected red blood cells and attacking more of them.

One strategy used by the pathogen to amplify its spreading probability is the formation of rosette-shaped clusters of uninfected erythrocytes surrounding a malaria-infected red blood cell. Since the parasite in the central cell of the rosette can easily infect the surrounding cells, the rosette enhances the infection. Moreover, rosetting is associated with severe malaria and high fever. In small blood vessels big rosettes bind to the walls of the capillaries, obstructing the normal blood flow, causing the body to react with high fever. Since children and elderly people have thinner capillaries, they are at higher risk of severe malaria.

One of the key players in the formation of the rosette is the protein PfEMP1, Plasmodium falciparum erythrocyte membrane protein-1. PfEMP1 sticks out of the infected red blood cell and deceives one of the first defenses against malaria called the IgM antibodies. IgMs bind to the pathogen or pathogen-infected cells and call other immune molecules, like the complement system, for backup. OIST researchers have shown that the IgM bind one or two PfEMP1 proteins, forming a bouquet type shape on the surface of the infected cells. The malaria parasite exploits these IgM to its own advantage, because the bouquet attracts more red blood cells facilitating the formation of rosettes. Moreover, the IgMs in the bouquet are not able to bind the complement system and to destroy the infected cell. "The bond between PfEMP1s and IgMs is like the perfect velcro: not too loose, not too strong. It is devilish engineered to fool our immune system," comments Prof. Skoglund.

The technique used by OIST researchers allows them to have a unique dynamic view of the proteins' conformation. "We have seen that PfEMP1 is a stiff C-shaped protein. Being stiff is an advantage, if it was floppy, it would not work so well. IgM, instead, assume three conformations: extended, bell and turtle shape".

Having this 3D structural model of the PfEMP1 and IgM complex can help scientists to design anti-malaria pharmacological treatments that can break down or wash out malaria rosettes without hurting the patient.
-end-


Okinawa Institute of Science and Technology (OIST) Graduate University

Related Immune System Articles:

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
First impressions go a long way in the immune system
An algorithm that predicts the immune response to a pathogen could lead to early diagnosis for such diseases as tuberculosis
Filming how our immune system kill bacteria
To kill bacteria in the blood, our immune system relies on nanomachines that can open deadly holes in their targets.
Putting the break on our immune system's response
Researchers have discovered how a tiny molecule known as miR-132 acts as a 'handbrake' on our immune system -- helping us fight infection.
Decoding the human immune system
For the first time ever, researchers are comprehensively sequencing the human immune system, which is billions of times larger than the human genome.
Masterswitch discovered in body's immune system
Scientists have discovered a critical part of the body's immune system with potentially major implications for the treatment of some of the most devastating diseases affecting humans.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.