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.
View: Text | PDF
Research Article Immunology Infectious disease

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

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

×

Figure 2

Expression of miR15a-3p, miR30c-5p, and miR30e-5p during P. falciparum blood-stage infection inversely correlates with parasite burden.

Options: View larger image (or click on image) Download as PowerPoint
Expression of miR15a-3p, miR30c-5p, and miR30e-5p during P. falciparum b...
Whole blood was collected prior to, and on days 4 and 7 of infection into PAXgene blood RNA tubes. Relative quantification of miR15a-3p, miR30c-5p, and miR30e-5p at day 4 (d4) and day 7 (d7) of infection (compared with day 0) was determined by RT-qPCR using Taqman microRNA assays and the ddCt method. Total parasite burden during the first 7 days of infection was defined as the AUC of the log-transformed parasite levels measured using a consensus P. falciparum qPCR assay from day 0 to day 7 of infection. Correlation between parasite burden and the relative average expression of miR15a-3p, miR30c-5p, and miR30e5p (A) at day 4 or day 7 of infection or (B) the average of fold changes for miR15a-3p, miR30c-5p, and miR30e-5p (miR signature). Parasite burden and miR expression datasets were log transformed for graphic representation and linear regression analysis. (C) Volunteers were classified as low-miR responders (n = 9 volunteers, average fold change ≤ 1) or high-miR responders (n = 11 volunteers, average fold change ≥ 1.5) according to the combined relative expression of miR15a-3p, miR30c-5p, and miR30e-5p at day 4 and day 7 of infection. One volunteer whose overall fold change was between 1 and 1.5 was not classified as a high- or low-miR responder, and was therefore excluded. Graphs show data from 21 volunteers (each depicted as a colored square across the x axis) from 4 independent cohorts.