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JCI Insight. 2017 Aug 3;2(15). pii: 93434. doi: 10.1172/jci.insight.93434. [Epub ahead of print]

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

Author information

1
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
2
The University of Queensland, Brisbane, Queensland, Australia.
3
Menzies School of Health Research, Darwin, Northern Territory, Australia.
4
Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia.
5
Department of Microbiology, Monash University, Victoria, Australia.
6
Centre for Biosecurity and Tropical Infectious Diseases, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.

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.

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