Severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes.
Severe malarial anemia (SMA) is the most frequent life-threatening complication of malaria and may contribute to the majority of malarial deaths worldwide. To explore the mechanisms of pathogenesis, we developed a novel murine model of SMA in which parasitemias peaked around 1.0% of circulating red blood cells (RBCs) and yet hemoglobin levels fell to 47% to 56% of baseline. The severity of anemia was independent of the level of peak or cumulative parasitemia, but was linked kinetically to the duration of patent infection. In vivo biotinylation analysis of the circulating blood compartment revealed that anemia arose from accelerated RBC turnover. Labeled RBCs were reduced to 1% of circulating cells by 8 days after labeling, indicating that the entire blood compartment had been turned over in approximately one week. The survival rate of freshly transfused RBCs was also markedly reduced in SMA animals, but was not altered when RBCs from SMA donors were transferred into naive recipients, suggesting few functional modifications to target RBCs. Anemia was significantly alleviated by depletion of either phagocytic cells or CD4+ T lymphocytes. This study demonstrates that immunologic mechanisms may contribute to SMA by promoting the accelerated turnover of uninfected RBCs.
Evans
Krystal J
KJ
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Hansen
Diana S
DS
van Rooijen
Nico
N
Buckingham
Lynn A
LA
Schofield
Louis
L
D000740:Anemia / Q000150:complications / Q000276:immunology* / Q000473:pathology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008288:Malaria / Q000150:complications / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar