Distilled database identifies genetic links to rare diseases
24 March 2023
Published online 18 June 2021
Some children produce higher levels of steroids in response to malaria infection, weakening their immune response.
Scientists have found an association between malaria infection and blood levels of naturally produced steroids in two ethnic groups of African children. Higher steroid levels in some children enhance their vulnerability to malaria by altering their immune responses.
The findings shed light on the molecular mechanisms at play during malaria and help explain some children’s higher susceptibility to this disease.
“In this study we identified molecules and pathways induced by host infection that can be targeted by existing or new drugs to complement malaria therapies,” says geneticist and lead researcher Youssef Idaghdour from New York University of Abu Dhabi in the United Arab Emirates.
Malaria is caused by infection with the parasite Plasmodium falciparum. To better understand how this parasite interacts with children’s immune systems, the researchers measured metabolite blood levels before and during malaria in children of the Gouin and Fulani ethnic groups of Burkina Faso in West Africa.
The team, which included researchers from the United States and Burkina Faso, discovered that malaria infection caused major changes in the children’s lipid and amino acid levels.
Blood steroid levels also changed, with an association found between their elevation in Gouin children and a strong suppression of immune response to malaria. “Higher steroid levels help the parasites evade the host’s immune response by inhibiting the activation and proliferation of T cells, specific immune cells that target the parasites,” explains Idaghdour. This, he says, allows the parasites to proliferate and invade more blood cells while scavenging host resources, such as lipids and other molecules.
In contrast, steroid levels in Fulani children did not rise in the same way, contributing to their stronger immune response to malaria and making them less susceptible to the disease.
Next, the researchers want to investigate why steroid levels don’t rise in Fulani children during malaria.
Abdrabou, W. et al. Metabolome modulation of the host adaptive immunity in human malaria. Nat. Metabol. https://doi.org/10.1038/s42255-021-00404-9 (2021).