Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis

Autor: Nabih Azar, Rafael M Martins, Prativa Kumari Behera, Audrey Lorthiois, Amanda K. A. Silva, Jose-Juan Lopez-Rubio, Gaelle Neveu, Pradeep Annamalai Subramani, Florence Gazeau, Catherine Lavazec, Dominique Mazier, Benjamin Marcel-Zerrougui, Samuel C. Wassmer, Sanghamitra Satpathi, Cyrielle Richard, Patrice Vallin, Aruna Mukti Minz, Frédérique Verdier, Muriel Andrieu, Florian Dupuy, Fiona Volpe
Přispěvatelé: Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), ispat general hospital [Rourkela, India] (IGH), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, CNRS UMR 7057 - Laboratoire Matières et Systèmes Complexes (MSC) (MSC), Centre National de la Recherche Scientifique (CNRS), LPHI - Laboratory of Pathogen Host Interactions (LPHI), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Pasteur [Paris], Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Hi-Tech Medical College [Rourkela, India], Institut National de la Santé et de la Recherche Médicale (INSERM), London School of Hygiene and Tropical Medicine (LSHTM), This work was supported by Cnrs, Inserm, the French Ministère de l’Enseignement Supérieur et de la Recherche and the Laboratory of Excellence GR-Ex, reference ANR-11-LABX-0051, funded by the IdEx program 'Investissements d’avenir' of the French National Research Agency, reference ANR-18-IDEX0001 (to GN, CL and FV). This study was also funded by the Fondation pour la Recherche Médicale under award number 'Equipe FRM' EQ20170336722 (to CL), the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number U19AI089676 (to SCW), and the UK Medical Research Council under award number MR/S009450/1 (to SCW). This work was partly supported by the French Parasitology consortium grant ParaFrap (ANR‐11‐LABX0024) to DM and PAS was supported by an ANR grant 'HypEpicC' to DM., The authors acknowledge the CYBIO Flow Cytometry core facility, the IMAG’IC imaging core facility and the Electron microscopy core facility of the Institut Cochin for technical help. The Electron Microscopy work was also carried out at ICM-QUANT Bioimaging core facility, ICM-Hospital Pitié Salpêtrière, Paris. We are grateful to Odile Mercereau-Puijalon and Micheline Guillotte for providing the anti-Pf11-1 antibodies and the VarO parasite line. We thank Jayamalini Jeremias for technical support. We thank Naomi Taylor, Silvia Portugal, Laurent Renia, Bjorn Kafsack, Robert Ménard and Frédéric Ariey for fruitful discussions., ANR-11-IDEX-0005-02/11-LABX-0051,GR-Ex,Biogenèse et pathologies du globule rouge(2011), ANR: 11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), ANR-14-CE16-0013,HypEpiC,Développement d'une nouvelle stratégie 'wake and kill' pour une cure radicale basée sur le contrôle épigénétique de la quiescence des hypnozoïtes de Plasmodium(2014), Université de Paris (UP), Lorthiois, Audrey, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, Appel à projets générique - Développement d'une nouvelle stratégie 'wake and kill' pour une cure radicale basée sur le contrôle épigénétique de la quiescence des hypnozoïtes de Plasmodium - - HypEpiC2014 - ANR-14-CE16-0013 - Appel à projets générique - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Adult
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology
Erythroblasts
Iron
[SDV]Life Sciences [q-bio]
Immunology
Plasmodium falciparum
Red Cells
Biochemistry
Plasmodium
Host-Parasite Interactions
03 medical and health sciences
Young Adult
0302 clinical medicine
Nucleated cell
Bone Marrow
parasitic diseases
medicine
Gametocyte
Humans
Erythropoiesis
[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Malaria
Falciparum
Cells
Cultured
ComputingMilieux_MISCELLANEOUS
biology
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Cell Biology
Hematology
medicine.disease
biology.organism_classification
3. Good health
Cell biology
[SDV] Life Sciences [q-bio]
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
Bone marrow
Malaria
[SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Zdroj: Blood
Blood, American Society of Hematology, 2020, Online ahead of print, ⟨10.1182/blood.2019004746⟩
Blood, American Society of Hematology, 2020, 136 (12), pp.1381-1393. ⟨10.1182/blood.2019004746⟩
Blood, 2020, Online ahead of print (12), pp.1381-1393. ⟨10.1182/blood.2019004746⟩
Blood, American Society of Hematology, 2020, Online ahead of print (12), pp.1381-1393. ⟨10.1182/blood.2019004746⟩
ISSN: 0006-4971
1528-0020
Popis: Plasmodium falciparum gametocytes, the sexual stage responsible for malaria parasite transmission from humans to mosquitoes, are key targets for malaria elimination. Immature gametocytes develop in the human bone marrow parenchyma, where they accumulate around erythroblastic islands. Notably though, the interactions between gametocytes and this hematopoietic niche have not been investigated. Here, we identify late erythroblasts as a new host cell for P falciparum sexual stages and show that gametocytes can fully develop inside these nucleated cells in vitro and in vivo, leading to infectious mature gametocytes within reticulocytes. Strikingly, we found that infection of erythroblasts by gametocytes and parasite-derived extracellular vesicles delay erythroid differentiation, thereby allowing gametocyte maturation to coincide with the release of their host cell from the bone marrow. Taken together, our findings highlight new mechanisms that are pivotal for the maintenance of immature gametocytes in the bone marrow and provide further insights on how Plasmodium parasites interfere with erythropoiesis and contribute to anemia in malaria patients.
Databáze: OpenAIRE
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