Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration

TLDR

Sequestration of malaria‑infected erythrocytes in organ microvasculature is believed to drive pathology, and cerebral malaria has been linked to PfEMP1‑mediated sequestration. The study aims to develop a real‑time in vivo imaging system using luciferase‑expressing Plasmodium berghei parasites to investigate malaria sequestration and its contribution to disease. The authors employed transgenic luciferase‑expressing P. berghei parasites to perform real‑time in vivo imaging of sequestration in mice.

Abstract

Sequestration of malaria-parasite-infected erythrocytes in the microvasculature of organs is thought to be a significant cause of pathology. Cerebral malaria (CM) is a major complication of Plasmodium falciparum infections, and PfEMP1-mediated sequestration of infected red blood cells has been considered to be the major feature leading to CM-related pathology. We report a system for the real-time in vivo imaging of sequestration using transgenic luciferase-expressing parasites of the rodent malaria parasite Plasmodium berghei. These studies revealed that: ( i ) as expected, lung tissue is a major site, but, unexpectedly, adipose tissue contributes significantly to sequestration, and ( ii ) the class II scavenger-receptor CD36 to which PfEMP1 can bind is also the major receptor for P. berghei sequestration, indicating a role for alternative parasite ligands, because orthologues of PfEMP1 are absent from rodent malaria parasites, and, importantly, ( iii ) cerebral complications still develop in the absence of CD36-mediated sequestration, dissociating parasite sequestration from CM-associated pathology. Real-time in vivo imaging of parasitic processes may be used to evaluate the molecular basis of pathology and develop strategies to prevent pathology.