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Dichotomous miR expression and immune responses following primary blood-stage malaria
Julie G. Burel, … , James S. McCarthy, Denise L. Doolan
Julie G. Burel, … , James S. McCarthy, Denise L. Doolan
Published August 3, 2017
Citation Information: JCI Insight. 2017;2(15):e93434. https://doi.org/10.1172/jci.insight.93434.
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Research Article Immunology Infectious disease

Dichotomous miR expression and immune responses following primary blood-stage malaria

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Abstract

Clinical responses to infection or vaccination and the development of effective immunity are characterized in humans by a marked interindividual variability. To gain an insight into the factors affecting this variability, we used a controlled human infection system to study early immune events following primary infection of healthy human volunteers with blood-stage Plasmodium falciparum malaria. By day 4 of infection, a dichotomous pattern of high or low expression of a defined set of microRNAs (miRs) emerged in volunteers that correlated with variation in parasite growth rate. Moreover, high-miR responders had higher numbers of activated CD4+ T cells, and developed significantly enhanced antimalarial antibody responses. Notably, a set of 17 miRs was identified in the whole blood of low-miR responders prior to infection that differentiated them from high-miR responders. These data implicate preexisting host factors as major determinants in the ability to effectively respond to primary malaria infection.

Authors

Julie G. Burel, Simon H. Apte, Penny L. Groves, Michelle J. Boyle, Christine Langer, James G. Beeson, James S. McCarthy, Denise L. Doolan

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Figure 1

Whole-blood miR expression profile in malaria-naive human volunteers experimentally infected with blood-stage P. falciparum.

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Whole-blood miR expression profile in malaria-naive human volunteers exp...
Whole blood was collected prior to, and on days 4 and 7 of infection in PAXgene blood RNA tubes. Relative quantification of 71 miRs involved in T cell and B cell activation detected at day 4 (d4) and day 7 (d7) of infection (compared to day 0) was determined by RT-qPCR using human T cell and B cell activation miScript miRNA PCR arrays (Qiagen) and the ddCt method. (A) Heatmaps representing the fold change in miR expression at d4 and d7 of infection relative to d0 for each miR across 14 volunteers from 3 independent cohorts. miRs were sorted according to their order within the miScript PCR array layout. (B) Correlation for each volunteer between the sum of fold changes for each of the 71 miRs’ expression at d4 or d7 after infection (relative to d0), determined using Pearson’s correlation test.

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