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.
Julie G. Burel, Simon H. Apte, Penny L. Groves, Michelle J. Boyle, Christine Langer, James G. Beeson, James S. McCarthy, Denise L. Doolan
Correlation of miR and mRNA expression levels. Expression levels of the 3-miR signature (miR15a-3p, miR30c-5p, and miR30e-5p) and the set of mRNAs shown to be significantly regulated between the high- and low-miR responder groups prior to infection (above in Table 2) were correlated at d0 and d7 (Spearman correlation, 6 volunteers from each of the high- and low-responder groups)