Plasmodium-infected erythrocytes induce secretion of IGFBP7 to form type II rosettes and escape phagocytosis
- Agency for Science, Technology and Research (A*STAR), Singapore
- University of Otago, New Zealand
- Australian National University, Australia
- INSERM, France
- University of Malaya, Malaysia
- Mahidol University, Thailand
- Cited 2
- Views 1,327
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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.
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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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