The immune system of mice is implicated in helping malaria to move from the blood to the brain

May 6, 2016, Agency for Science, Technology and Research (A*STAR), Singapore
The immune system of mice is implicated in helping malaria to move from the blood to the brain
An endothelial cell (blue oval) from a mouse brain in culture that has taken up two types of parasite material (green and black particles). Credit: Modified from Ref.1 and licensed under CC-BY-4.0 © 2015 Howland et al.

By studying malaria in mice, three A*STAR researchers have discovered how malaria parasites in the bloodstream can affect the brain, causing a life-threatening condition called cerebral malaria.

Cerebral malaria is a complication that arises from the most dangerous form of the blood disease. It is the main cause of death from malaria and kills hundreds of thousands of children in Africa every year.

Since malaria is a blood-borne disease, the brain should be isolated from it by the blood–brain barrier, which restricts the transfer of certain compounds from the blood to the brain. It was not clear how this barrier is breached in cases of cerebral malaria.

Now, Shanshan Howland, Chek Meng Poh and Laurent Rénia of the Singapore Immunology Network have shown how malaria breaks through the blood–brain barrier in mice.

They discovered that cells that line the , known as , take up material from malaria-infected coursing through the blood vessels in the mice's brains. These endothelial cells then 'display' small fragments of proteins (peptides) derived from the parasite on their surfaces (see image). This means the peptides act as targets for the body's immune system, which mistakes them for parasitic cells. In particular, they are attacked by known as killer T cells, and in this way the blood–brain barrier is broken down, often with fatal results.

A similar process may occur in humans ― the researchers showed that endothelial cells from the human brain grown in culture also take up in a similar way. But to conclusively prove this connection will require ascertaining whether there are any equivalent peptides with the same function in humans.

The finding has the potential to save lives. "Right now, the only treatment available is anti malarial drugs to kill the parasites, and the mortality rate in African children can be around 20 per cent even with treatment. Children often die within a day or two of entering hospital," says Howland. "If we can block presentation of peptides by endothelial cells or the immune recognition of such, it could buy time for anti malarials to clear the parasites."

The discovery is significant for other serious neurological diseases besides . "The ability to display peptides from pathogens is generally restricted to specialized immune cells, but our study has shown for the first time that brain endothelial cells can also do the same," explains Howland. "This has important implications for multiple sclerosis, encephalitis and meningitis."

Explore further: Brain-damaging complications of malaria arise from immune response to parasite antigens absorbed by blood vessels

More information: Shanshan W. Howland et al. Activated Brain Endothelial Cells Cross-Present Malaria Antigen, PLOS Pathogens (2015). DOI: 10.1371/journal.ppat.1004963

Related Stories

Brain-damaging complications of malaria arise from immune response to parasite antigens absorbed by blood vessels

September 11, 2013
Most deaths caused by the malarial parasite Plasmodium falciparum result from the onset of cerebral malaria. This severe neurological condition arises when parasites accumulate within the brain vasculature. Numerous studies ...

Patterns of brain swelling may explain susceptibility of children to cerebral malaria

March 10, 2016
Brain swelling is a strong predictor of death in children with cerebral malaria (a severe form of the disease where parasites have accumulated in brain vessels), and also in mice with experimental cerebral malaria (ECM). ...

Blood pressure build-up from white blood cells may cause cerebral malaria death

December 4, 2014
Intracranial hypertension—increased blood pressure inside the head—can predict a child's risk of death from malaria. A study published on December 4th in PLOS Pathogens reports that accumulation of white blood cells impairs ...

Genes linked with malaria's virulence shared by apes, humans

October 12, 2015
The malaria parasite molecules associated with severe disease and death—those that allow the parasite to escape recognition by the immune system—have been shown to share key gene segments with chimp and gorilla malaria ...

How the immune system prevents repeated malaria fever episodes in highly exposed children

April 17, 2014
Children in Mali (and many other regions where malaria is common) are infected with malaria parasites more than 100 times a year, but they get sick with malaria fever only a few times. To understand how the immune system ...

Reducing infectious malaria parasites in donated blood could help prevent transmission

April 21, 2016
A technique for reducing the number of infectious malaria parasites in whole blood could significantly reduce the number of cases of transmission of malaria through blood transfusion, according to a collaboration between ...

Recommended for you

Basic research in fruit flies leads to potential drug for diseases afflicting millions

July 13, 2018
River blindness and elephantiasis are debilitating diseases caused by parasitic worms that infect as many as 150 million people worldwide. They are among the "neglected tropical diseases" for which better treatments are desperately ...

Light based cochlear implant restores hearing in gerbils

July 12, 2018
A team of researchers with members from a variety of institutions across Germany has developed a new type of cochlear implant—one based on light. In their paper published in the journal Science Translational Medicine, the ...

Researchers discover gene that controls bone-to-fat ratio in bone marrow

July 12, 2018
In an unexpected discovery, UCLA researchers have found that a gene previously known to control human metabolism also controls the equilibrium of bone and fat in bone marrow as well as how an adult stem cell expresses its ...

Intensive care patients' muscles unable to use fats for energy

July 12, 2018
The muscles of people in intensive care are less able to use fats for energy, contributing to extensive loss of muscle mass, finds a new study co-led by UCL, King's College London and Guy's and St Thomas' NHS Foundation Trust.

Blood biomarker can help predict disease progression in patients with COPD

July 12, 2018
Some patients with COPD demonstrate signs of accelerated aging. In a new study published in the journal CHEST researchers report that measuring blood telomeres, a marker of aging of cells, can be used to predict future risk ...

Rogue molecules provoke out-of-control scar tissue, strangle organs

July 12, 2018
Normal scar tissue forms to heal an internal wound and quietly retreats when the job is done. But in many common diseases—kidney, liver and lung fibrosis—the scar tissue goes rogue and strangles vital organs. These diseases ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.