Abstract
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.
Data availability
All sample/data information in this study are included in the manuscript and supporting files (Supplementary files, Source data files). Of note, data represented as bar graphs are provided as source data tables (5 sets): Figure 1-Source data 1; Figure 5-Source data 1; Figure5-Source data 2; Figure 8- Source data 1; Figure 8- Source data 2
Article and author information
Author details
Funding
Agency for Science, Technology and Research (SIgN core funding)
- Wenn-Chyau Lee
- Khairunnisa Ghaffar
- Shanshan W Howland
- Subhra Biswas
- Benoit Malleret
- Laurent Renia
Agency for Science, Technology and Research (JCO-DP BMSI/15-800006-SIGN)
- Laurent Renia
Open Fund-Young Individual Research Grant, National Medical Research Council, Ministry of Health, Singapore (OF-YIRG NMRC/OFYIRG/0070/2018)
- Wenn-Chyau Lee
University of Malaya High Impact Research Grant (UM.C/HIR/MOHE/MED/16)
- Yee-Ling Lau
Agency for Science, Technology and Research (IMCB Core funding)
- Radoslaw Mikolaj Sobota
Agency for Science, Technology and Research (Young Investigator Grant YIG 2015)
- Radoslaw Mikolaj Sobota
Wellcome Trust (SMRU is part of the Mahidol-Oxford University Research Unit)
- Cindy Chu
- François Nosten
NUHS start-up funding (NUHSRO/2018/006/SU/01)
- Benoit Malleret
NUHS seed fund (NUHRO/2018/094/T1)
- Benoit Malleret
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Urszula Krzych, Walter Reed Army Institute of Research, United States
Publication history
- Received: September 2, 2019
- Accepted: January 27, 2020
- Accepted Manuscript published: February 18, 2020 (version 1)
- Version of Record published: February 28, 2020 (version 2)
Copyright
© 2020, Lee et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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