Stage-dependent fate of Plasmodium falciparum-infected red blood cells in the spleen and sickle-cell trait-related protection against malaria.

Autor: Diakité SA; INSERM U1134, Paris 5, Paris 7, Institut National de la Transfusion Sanguine, 75015, Paris, France.; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odontostomatology, University of Bamako, Bamako, BP, 1805, Mali.; Laboratoire d'Excellence du Globule Rouge (GR-Ex), 75115, Paris, France., Ndour PA; INSERM U1134, Paris 5, Paris 7, Institut National de la Transfusion Sanguine, 75015, Paris, France.; Laboratoire d'Excellence du Globule Rouge (GR-Ex), 75115, Paris, France., Brousse V; Centre de Référence de la Drépanocytose, Hôpital Universitaire Necker Enfants Malades, 75012, Paris, France., Gay F; INSERM U1134, Paris 5, Paris 7, Institut National de la Transfusion Sanguine, 75015, Paris, France., Roussel C; INSERM U1134, Paris 5, Paris 7, Institut National de la Transfusion Sanguine, 75015, Paris, France., Biligui S; INSERM U1134, Paris 5, Paris 7, Institut National de la Transfusion Sanguine, 75015, Paris, France., Dussiot M; Laboratoire d'Excellence du Globule Rouge (GR-Ex), 75115, Paris, France.; INSERM U1163/CNRS ERL 8254, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Institut Imagine, Université Paris Descartes-Sorbonne Paris Cité, Paris, France., Prendki V; INSERM U1134, Paris 5, Paris 7, Institut National de la Transfusion Sanguine, 75015, Paris, France., Lopera-Mesa TM; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA., Traoré K; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odontostomatology, University of Bamako, Bamako, BP, 1805, Mali., Konaté D; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odontostomatology, University of Bamako, Bamako, BP, 1805, Mali., Doumbia S; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odontostomatology, University of Bamako, Bamako, BP, 1805, Mali., Cros J; Department of Chirurgie Digestive et Viscérale, Hôpital Beaujon, AP-HP, 92110, Clichy, France., Dokmak S; Department of Chirurgie Digestive et Viscérale, Hôpital Beaujon, AP-HP, 92110, Clichy, France., Fairhurst RM; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA., Diakité M; Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odontostomatology, University of Bamako, Bamako, BP, 1805, Mali., Buffet PA; INSERM U1134, Paris 5, Paris 7, Institut National de la Transfusion Sanguine, 75015, Paris, France. pabuffet@gmail.com.; Laboratoire d'Excellence du Globule Rouge (GR-Ex), 75115, Paris, France. pabuffet@gmail.com.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2016 Sep 21; Vol. 15 (1), pp. 482. Date of Electronic Publication: 2016 Sep 21.
DOI: 10.1186/s12936-016-1522-0
Abstrakt: Background: Sickle-cell trait (HbAS) reduces falciparum malaria risk and suppresses parasitaemia. Although several candidate mechanisms have been proposed, their epidemiological, clinical and experimental correlates have not been adequately explained. To explore the basis for generally lower parasitaemias and delayed malaria episodes in children with HbAS, it is hypothesized here that their spleen-dependent removal of ring-infected red blood cells (RBCs) is more efficient than in children with normal haemoglobin A (HbAA).
Methods: The mechanical splenic retention of Plasmodium falciparum-infected RBCs from subjects with HbAS or HbAA was investigated using two physiologically relevant methods: microsphiltration and ex vivo spleen perfusion. P. falciparum-infected RBCs obtained from in vitro cultures and from patients were used in either normoxic or hypoxic conditions. The effect of sickling in ring-infected HbAS RBCs was also investigated.
Results: When a laboratory-adapted parasite strain was analysed, ring-infected HbAA RBCs were retained in microsphilters at similar or greater levels than ring-infected HbAS RBCs, under normoxic (retention rate 62.5 vs 43.8 %, P < 0.01) and hypoxic (54.0 vs 38.0 %, P = 0.11) conditions. When parasitized RBCs from Malian children were analysed, retention of ring-infected HbAA and HbAS RBCs was similar when tested either directly ex vivo (32.1 vs 28.7 %, P = 0.52) or after one re-invasion in vitro (55.9 vs 43.7 %, P = 0.30). In hypoxia, sickling of uninfected and ring-infected HbAS RBCs (8.6 vs 5.7 %, P = 0.51), and retention of ring-infected HbAA and HbAS RBCs in microsphilters (72.5 vs 68.8 %, P = 0.38) and spleens (41.2 vs 30.4 %, P = 0.11), also did not differ. Retention of HbAS and HbAA RBCs infected with mature P. falciparum stages was greater than 95 %.
Conclusions: Sickle-cell trait is not associated with higher retention or sickling of ring-infected RBCs in experimental systems reflecting the mechanical sensing of RBCs by the human spleen. As observed with HbAA RBCs, HbAS RBCs infected with mature parasites are completely retained. Because the cytoadherence of HbAS RBCs infected with mature parasites is impaired, the very efficient splenic retention of such non-adherent infected RBCs is expected to result in a slower rise of P. falciparum parasitaemia in sickle-cell trait carriers.
Databáze: MEDLINE
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