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

PLoS Pathogens, vol. 17, pp. e1010114

Abstract

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 RT-qPCR. 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.

Authors 13

1. Hendrik Possemiers

   Rega Institute for Medical Research · KU Leuven

   Affiliation as printed

   Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

2. Thao‐Thy Pham

   Rega Institute for Medical Research · Instituut voor Tropische Geneeskunde · KU Leuven

   Affiliation as printed

   Currently at Clinical Immunology Unit, Department of Clinical Sciences, Institute of Tropical Medicine Antwerp, Belgium

   Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

3. Marion Coens

   Rega Institute for Medical Research · KU Leuven

   Affiliation as printed

   Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

4. Emilie Pollenus

   Rega Institute for Medical Research · KU Leuven

   Affiliation as printed

   Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

5. Sofie Knoops

   Rega Institute for Medical Research · KU Leuven

   Affiliation as printed

   Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

6. Sam Noppen

   Rega Institute for Medical Research · KU Leuven

   Affiliation as printed

   Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

7. Leen Vandermosten

   Rega Institute for Medical Research · KU Leuven

   Affiliation as printed

   Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

8. Sigrid D’haese

   Vrije Universiteit Brussel · Rega Institute for Medical Research · KU Leuven

   Affiliation as printed

   Currently at Neuro-Aging & Viro-Immunotherapy (NAVI), Vrije Universiteit Brussel (VUB), Brussels, Belgium

   Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

9. Luna Dillemans

   Rega Institute for Medical Research · KU Leuven

   Affiliation as printed

   Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

10. Fran Prenen

    Rega Institute for Medical Research · KU Leuven

    Affiliation as printed

    Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

11. Dominique Schols

    Rega Institute for Medical Research · KU Leuven

    Affiliation as printed

    Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium

12. Blandine M. D. Franke-Fayard Aachen Department of Parasitology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Parasitology, Leiden University Medical Center, The Netherlands

13. Philippe E. Van den Steen corresponding

    Rega Institute for Medical Research · KU Leuven

    Affiliation as printed

    Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical research, KU Leuven, Belgium