Plasmodium-infected erythrocytes induce secretion of IGFBP7 to form type II rosettes and escape phagocytosis

Wenn-Chyau Lee , Bruce Russell , Radoslaw Mikolaj Sobota , Khairunnisa Ghaffar , Shanshan Howland , Zi Xin Wong , Alexander Maier , Dominique Dorin-Semblat , Subhra Biswas , Benoit Gamain (1) , Yee-Ling Lau , Benoit Malleret , Cindy Chu , François Nosten , Laurent Renia

1 BIGR (UMR_S_1134 / U1134) - Biologie Intégrée du Globule Rouge

In malaria, rosetting is described as a phenomenon where an infected erythrocyte (IRBC) is attached to uninfected erythrocytes (URBC). In some studies, rosetting has been associated with malaria pathogenesis. Here, we have identified a new type of rosetting. Using a step-by-step approach, we identified IGFBP7, a protein secreted by monocytes in response to parasite stimulation, as a rosette-stimulator for Plasmodium falciparum-and P. vivax-IRBC. IGFBP7mediated rosette-stimulation was rapid yet reversible. Unlike type I rosetting that involves direct interaction of rosetting ligands on IRBC and receptors on URBC, the IGFBP7-mediated, type II rosetting requires two additional serum factors, namely von Willebrand factor and thrombospondin-1. These two factors interact with IGFBP7 to mediate rosette formation by the IRBC. Importantly, the IGFBP7-induced type II rosetting hampers phagocytosis of IRBC by host phagocytes.

Domaines: Sciences du Vivant [q-bio]

Wenn-Chyau Lee, Bruce Russell, Radoslaw Mikolaj Sobota, Khairunnisa Ghaffar, Shanshan Howland, et al.. Plasmodium-infected erythrocytes induce secretion of IGFBP7 to form type II rosettes and escape phagocytosis. eLife, 2020, 9, ⟨10.7554/eLife.51546⟩. ⟨hal-02941720⟩