Scientists at National Institute of Health (NIH) have discovered that certain immune cells (T cells) in the body can play a vital role in combating the devastating effects of cerebral malaria in children. These immune cells can be targeted and harnessed with the help of drugs.
“This is the first study showing that T cells target blood vessels in brains of children with cerebral malaria,” says Dorian McGavern, Ph.D., head of NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and co-author of the study.
“These findings build a bridge between mouse and human cerebral malaria studies by implicating T cells in the development of disease pathology in children. It is well established that T cells cause the brain vasculature injury associated with cerebral malaria in mice, but this was not known in humans.”
Cerebral malaria is a subset of malaria that affects more than 200 million people annually, most of whom are children. The parasite (plasmodium) flourishes in the liver and enters the brain blood vessels where it produces marked swelling. As a result, the cerebral pressure increases and leads to headache, delirium and coma. Although cerebral malaria is treated with quinine (antiviral), as many as 25% of the affected children succumb to death each year. Those who survive often end up with lifelong neurological complications such as cognitive impairment.
The researchers examined and compared brain tissue of 23 children dying of cerebral malaria to the tissue of 11 children dying from other causes. The samples were studied through state-of-the-art microscopy technique for the presence of cytotoxic lymphocytes (CTLs). CTLs are part of the body’s defense system that are activated when the body is attacked by a foreign agent.
The researchers found an increased concentration of CTLs in the brain blood vessels of cerebral malaria tissue samples. Microscopy also revealed presence of effector molecules released by the CTLs indicating that the latter play a major role in causing damage to the brain blood vessels in cerebral malaria.
Current clinical treatments of cerebral malaria typically focus on red blood cells which are thought to clog the blood vessels and increase cerebral pressure. The findings of the current study, as well as those in mouse models, continuously point toward the role of CTLs and insist why physicians should change their focus of treatment. Cerebral malaria, the researchers believe, has more to do with immunological response of the body than red cells. T-cells, in their attempt to fight the parasite, end up damaging the host’s brain blood vessels.
Keeping the results of the study in mind, Dr. McGavern and team ran parallel studies where they treated mice with molecules (drugs) targeting CTLs. They found the drug to prevent over 60% cases of fatal cerebral malaria in the mice.
Cerebral malaria is a complex disease; it has often been linked with HIV-co-infection. The investigators infected cerebral malaria tissue with HIV and compared it with HIV-negative tissue. In the HIV-positive tissue, CTLs could be seen in abundance crowding the outside of the blood vessels whereas in the HIV-negative sample, CTLs were limited to the lining of blood vessels.
The scientists are excited their findings will open realms of possible new treatments for children suffering from cerebral malaria. However, additional research is needed to further identify and confirm the role of T cells in human cerebral malaria.
The study was published in the Journal of Clinical Investigation on February 18, 2020.