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

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 4

The anti-Plasmodium antibody response is more robust in high-miR responders.

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The anti-Plasmodium antibody response is more robust in high-miR respond...
IgG antibody titers specific to (A) P. falciparum schizont extract (PfSE) or (B) MSP1-42 (42-kDa fragment of merozoite surface 1 [MSP1]) and MSP2 P. falciparum proteins were determined using an ELISA assay in plasma samples collected prior to infection and 28 ± 3 days after the day of infection. (C) IgG subclass responses (IgG1, IgG2, IgG3, and IgG4) were determined for MSP2. (D) Fold-change induction between d0 and d28 in antibody titers was calculated for each subclass against MSP2 and was compared between low- and high-miR responders. (E) IgM fold-change induction between d0 and d28 in response to MSP1, MSP2, MSP3, MSP4, MSP5, and MSP6 was compared between low- and high-miR responders. Data were assessed for significance by nonparametric paired Wilcoxon test (A–C) or nonparametric Mann-Whitney test (D and E). Box-and-whisker plots: boxes show 25th to 75th percentiles, whiskers extend to all data, line within box shows median; low-miR responders n = 9, high-miR responders n = 10. *P < 0.05; **P < 0.01. ns, not significant.