Wenn Chyau LeeBruce RussellRadoslaw Mikolaj SobotaKhairunnisa GhaffarShanshan W. HowlandZi Xin WongAlexander G. MaierDominique Dorin-SemblatSubhra BiswasBenoit GamainYee Ling LauBenoit MalleretCindy ChuFrançois NostenLaurent ReniaA-Star, Singapore Immunology NetworkUniversite Paris-SaclayUniversity of MalayaYong Loo Lin School of MedicineAgency for Science, Technology and Research, SingaporeA-Star, Institute of Molecular and Cell BiologyUniversity of OtagoInstitut National de la Transfusion SanguineMahidol UniversityAustralian National UniversityNuffield Department of Clinical Medicine2020-03-262020-03-262020-02-18eLife. Vol.9, (2020)2050084X2-s2.0-85081069101https://repository.li.mahidol.ac.th/handle/20.500.14594/53584© 2020, Lee et al. 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. IGFBP7-mediated 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyImmunology and MicrobiologyNeuroscienceArticleSCOPUS10.7554/eLife.51546