Malaria is still one of the most important infectious diseases. Its death toll is very high, especially in Africa. In 2016, no fewer than 216 million cases were identified worldwide, with 445,000 fatal outcomes. Malaria is caused by a parasite that is transmitted through the bite of an infected mosquito.
Various pathologies"Malaria is a complex disease appearing in varying degrees of severity," says Professor Philippe Van den Steen of the Laboratory of Immunobiology. "There is a very large group of people who are infected without becoming ill. The mild form of malaria causes clear clinical signs, and the severe or complicated form can be deadly. We are trying to better understand this complexity in our laboratory."
For her doctoral research, Leen Vandermosten studied four different mouse models of malaria pathologies, ranging from no to serious complications. She specifically investigated the role of the adrenal gland. Mice in which the adrenal gland was surgically removed proved to be strikingly less tolerant to malarial disease, compared to the control group with adrenal gland.
"The adrenal gland is vital to survive the infection," says Vandermosten. "That may sound logical, but previously we didn’t know how crucial this organ actually is. Whether there are many or few parasites, the host is unprotected against lethal disease without adrenal glands."
The metabolism of the host seems highly dependent on the adrenal gland. "Our research shows that malaria disturbs the sugar metabolism and that the adrenal gland is crucial to keep the situation under control. Without adrenal gland, the sugar level in the blood drops dramatically, and the sugar supply in the liver even gets entirely depleted. Consequently, the brain, which consumes a lot of sugar, cannot function anymore and survival becomes impossible."
The adrenal gland is a crucial regulator, not only for the metabolism, but also for the immune system. The adrenal hormones suppress the inflammation that is caused by malaria. The researchers saw this anti-inflammatory effect mainly in the brain and blood.
"We are exploring a new field with this study," continues Professor Van den Steen. "A lot of malaria research focuses on the immune and inflammatory responses in the host, but our results show that the sugar balance is equally important. Now, we have to further explore how the adrenal gland, the metabolism and the immune system are interconnected. Moreover, we definitely want to see whether these findings are also true for patients and whether they could possibly lead to applications in the future. But that is a long-term effort."
Journal articleNature Communications
"Adrenal hormones mediate disease tolerance in malaria"