Skeleton binding protein-1-mediated parasite sequestration inhibits spontaneous resolution of malaria-associated acute respiratory distress syndrome

Hendrik Possemiers, Thao-Thy Pham, Marion Coens, Emilie Pollenus, Sofie Knoops, Sam Noppen, Leen Vandermosten, Sigrid D'haese, Luna Dillemans, Fran Prenen, Dominique Schols, Blandine Franke-Fayard, Philippe E. Van den Steen

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Malaria is a hazardous disease caused by Plasmodium parasites and often results in lethal complications, including malaria-associated acute respiratory distress syndrome (MA-ARDS). Parasite sequestration in the microvasculature is often observed, but its role in malaria pathogenesis and complications is still incompletely understood. We used skeleton binding protein-1 (SBP-1) KO parasites to study the role of sequestration in experimental MA-ARDS. The sequestration-deficiency of these SBP-1 KO parasites was confirmed with bioluminescence imaging and by measuring parasite accumulation in the lungs with RTqPCR. The SBP-1 KO parasites induced similar lung pathology in the early stage of experimental MA-ARDS compared to wildtype (WT) parasites. Strikingly, the lung pathology resolved subsequently in more than 60% of the SBP-1 KO infected mice, resulting in prolonged survival despite the continuous presence of the parasite. This spontaneous disease resolution was associated with decreased inflammatory cytokine expression measured by RT-qPCR and lower expression of cytotoxic markers in pathogenic CD8(+) T cells in the lungs of SBP-1 KO infected mice. These data suggest that SBP-1-mediated parasite sequestration and subsequent high parasite load are not essential for the development of experimental MA-ARDS but inhibit the resolution of the disease.

Original languageEnglish
Article numbere1010114
JournalPLoS Pathogens
Issue number11
Number of pages27
Publication statusPublished - 2021


  • Animals
  • Disease Progression
  • Female
  • Lung/metabolism
  • Malaria/complications
  • Male
  • Membrane Proteins/deficiency
  • Mice
  • Mice, Inbred C57BL
  • Plasmodium berghei/pathogenicity
  • Protozoan Proteins/genetics
  • Respiratory Distress Syndrome/metabolism

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