Laurent RENIA -Executive Director Singapore Immunology Network – Agency for Science, Technology, and Research, Singapore
Malaria remains one of the most deadly infection in humans. After a successful invasion, malaria parasite Plasmodium parasites extensively remodels the infected erythrocyte cellular architecture, conferring to infected erythrocytes cytoadhesive properties. One of the interesting biological phenomena by late stage infected red blood cells (IRBC) of all malaria species is their capacity to form rosettes with non-infected RBC. This phenomenon that have been associated for P. falciparum with severity of the infection in some but not all studies. Here, we have characterized the rosetting prevalence of P. falciparum and P. vivax isolates from the Thai-Myanmar border, and found that factors derived from host’s monocytes stimulated with IRBC were capable of stimulating rosette formation. Insulin-like growth factor binding protein 7 (IGFBP7) in particular was the most potent factor for induction of rosettes. The IGFBP7-mediated rosetting in P. vivax and P. falciparum was compared. Subsequent experiments with laboratory-adapted P. falciparum lines revealed the complexity of IGFBP7-induced rosetting, which required involvement of another two host-derived factors, thrombospondin and Von Willebrand Factor. Importantly, this phenomenon hampers phagocytosis of the IRBCs, suggesting that the parasites use IGFBP7 as a signal to detect approaching monocytes/ macrophages, and form more rosettes to escape phagocytosis.