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Translocation of sickle cell erythrocyte microRNAs into plasmodium falciparum inhibits parasite rranslation and contributes to malaria resistance

Item Type:Article
Title:Translocation of sickle cell erythrocyte microRNAs into plasmodium falciparum inhibits parasite rranslation and contributes to malaria resistance
Creators Name:Lamonte, G. and Philip, N. and Reardon, J. and Lacsina, J.R. and Majoros, W. and Chapman, L. and Thornburg, C.D. and Telen, M.J. and Ohler, U. and Nicchitta, C.V. and Haystead, T. and Chi, J.T.
Abstract:Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes, and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite messenger RNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical miRNA activity, which may represent a unique host defense strategy against complex eukaryotic pathogens.
Keywords:Biological Transport, Cultured Cells, Down Regulation, Erythrocytes, Falciparum Malaria, MicroRNAs, Plasmodium falciparum, Protein Biosynthesis, Sickle Hemoglobin
Source:Cell Host & Microbe
ISSN:1931-3128
Publisher:Elsevier (The Netherlands)
Volume:12
Number:2
Page Range:187-199
Date:16 August 2012
Official Publication:https://doi.org/10.1016/j.chom.2012.06.007
PubMed:View item in PubMed

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