Red blood cells infected with P. Falciparum parasites. The Maurer’s Clefts (parasite-established sorting stations in the red blood cell) are stained in green and KAHRP (a protein into which the major parasite ligand PfEMP1 is embedded) in magenta, with the parasite’s nuclei in blue. Image credit: Stephanie Nofal (CC BY 4.0)
A fever usually indicates that the body is fighting an infection. In malaria, parasites infect red blood cells, and high temperature is a common symptom. Fever may slow parasite growth, but it may also increase levels of a parasite protein called PfEMP1 on the surface of infected cells. PfEMP1 makes these cells sticky, helping them attach to blood vessel walls and avoid removal by the spleen. This adhesion can worsen disease by blocking small blood vessels, including those in the brain. If the fever increases this stickiness, it could worsen symptoms. However, previous studies used to vary temperatures, leading to conflicting results.
Jones et al. tested whether a common fever temperature (39 °C) affects PfEMP1 levels and cell adhesion. Using infected human red blood cells, they found that 39 °C increases both adhesion to proteins found on blood vessel walls and the number of cells displaying PfEMP1 on their surface. To investigate the process behind this increase, they used techniques to measure the activity of proteins and their interactions with other human proteins. They showed that heat accelerates the export of certain parasite proteins to the red blood cell surface, including PfEMP1 and likely others, without increasing overall protein levels or parasite growth.
These findings suggest that fever may accelerate the surface export of certain parasite proteins, which unintentionally help infected cells adhere more strongly and earlier to blood vessels, potentially worsening the disease. However, further work is needed to confirm this in more realistic settings and to link it directly to disease severity in patients.
