Malaria Induces Anemia through CD8+ T Cell-Dependent Parasite Clearance and Erythrocyte Removal in the Spleen - Université Pierre et Marie Curie Accéder directement au contenu
Article Dans Une Revue mBio Année : 2015

Malaria Induces Anemia through CD8+ T Cell-Dependent Parasite Clearance and Erythrocyte Removal in the Spleen

Résumé

Severe malarial anemia (SMA) in semi-immune individuals eliminates both infected and uninfected erythrocytes and is a frequent fatal complication. It is proportional not to circulating parasitemia but total parasite mass (sequestered) in the organs. Thus, immune responses that clear parasites in organs may trigger changes leading to anemia. Here, we use an outbred-rat model where increasing parasite removal in the spleen escalated uninfected-erythrocyte removal. Splenic parasite clearance was associated with activated CD8+ T cells, immunodepletion of which prevented parasite clearance. CD8+ T cell repletion and concomitant reduction of the parasite load was associated with exacerbated (40 to 60%) hemoglobin loss and changes in properties of uninfected erythrocytes. Together, these data suggest that CD8+ T cell-dependent parasite clearance causes erythrocyte removal in the spleen and thus anemia. In children infected with the human malaria parasite Plasmodium falciparum, elevation of parasite biomass (not the number of circulating parasites) increased the odds ratio for SMA by 3.5-fold (95% confidence intervals [CI95%], 1.8- to 7.5-fold). CD8+ T cell expansion/activation independently increased the odds ratio by 2.4-fold (CI95%, 1.0- to 5.7-fold). Concomitant increases in both conferred a 7-fold (CI95%, 1.9- to 27.4-fold)-greater risk for SMA. Together, these data suggest that CD8+-dependent parasite clearance may predispose individuals to uninfected-erythrocyte loss and SMA, thus informing severe disease diagnosis and strategies for vaccine development.
Fichier principal
Vignette du fichier
mBio-2015-Safeukui-.pdf (3.49 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-01226353 , version 1 (09-11-2015)

Licence

Paternité - Pas d'utilisation commerciale - Partage selon les Conditions Initiales

Identifiants

Citer

Innocent Safeukui, Noé D. Gomez, Aanuoluwa A. Adelani, Florence Burte, Nathaniel K. Afolabi, et al.. Malaria Induces Anemia through CD8+ T Cell-Dependent Parasite Clearance and Erythrocyte Removal in the Spleen. mBio, 2015, 6 (1), pp.e02493-14. ⟨10.1128/mBio.02493-14⟩. ⟨hal-01226353⟩
72 Consultations
205 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More