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Immune variation leads to diverse outcomes in human malaria (2020-01-15)

Falciparum malaria is clinically heterogeneous and yet in most cases the risk of life-threatening disease dramatically declines after the first few infections of life because children rapidly acquire disease tolerance (resistance to severe malaria without improved control of parasite burden). Identifying the factors that determine clinical outcome in a malaria-naive host is therefore paramount to reduce malaria mortality. However, the relative contribution of disease-causing variants of the Plasmodium var gene family versus pathogenic inflammatory cytokine cascades remains fiercely debated - we sought to reconcile these conflicting arguments by studying their interaction in vivo. To this end, two human challenge models were used to reveal the parasite-host interactions that underpin variation in falciparum malaria. To capture the diversity of human immune responses, each individual was analysed independently by tracking dynamic changes in their whole blood transcriptome through time. And to uncover evidence of preferential expansion of disease-causing variants, var gene expression was tracked in vivo from the start to end of infection. In this way, we could show that group A var genes are always expressed upon liver egress but in a minority population that does not increase over 10-days of blood cycling; there is no selection of disease-causing variants in the naive host. In fact, parasites do not respond in any way to differences or changes in host environment. On the other hand, host-intrinsic variation determines the intensity of inflammation and progression to clinical malaria. And furthermore, regulation of the interferon signaling network controls host fate. These data emphasise the role of human immune decision-making in shaping course & outcome of infection. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ . This dataset contains all the data available for this study on 2020-01-15.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001003766 Transcriptome Analysis

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00003249228 cram 782.9 MB
EGAF00003249229 cram 811.6 MB
EGAF00003249230 cram 705.7 MB
EGAF00003249231 cram 809.1 MB
EGAF00003249232 cram 906.0 MB
EGAF00003249233 cram 897.9 MB
EGAF00003249234 cram 814.5 MB
EGAF00003249235 cram 720.6 MB
EGAF00003249236 cram 703.1 MB
EGAF00003249237 cram 777.2 MB
EGAF00003249238 cram 766.9 MB
EGAF00003249239 cram 858.7 MB
EGAF00003249240 cram 640.5 MB
EGAF00003249241 cram 741.1 MB
EGAF00003249242 cram 696.1 MB
EGAF00003249243 cram 782.2 MB
EGAF00003249244 cram 813.3 MB
EGAF00003249245 cram 706.8 MB
EGAF00003249246 cram 810.8 MB
EGAF00003249247 cram 909.6 MB
EGAF00003249248 cram 899.2 MB
EGAF00003249249 cram 817.0 MB
EGAF00003249250 cram 723.0 MB
EGAF00003249251 cram 704.9 MB
EGAF00003249252 cram 779.8 MB
EGAF00003249253 cram 770.9 MB
EGAF00003249254 cram 861.4 MB
EGAF00003249255 cram 642.5 MB
EGAF00003249256 cram 743.2 MB
EGAF00003249257 cram 698.6 MB
EGAF00003249258 cram 784.5 MB
EGAF00003249259 cram 814.6 MB
EGAF00003249260 cram 760.3 MB
EGAF00003249261 cram 929.2 MB
EGAF00003249262 cram 1.0 GB
EGAF00003249263 cram 786.2 MB
EGAF00003249264 cram 774.7 MB
EGAF00003249265 cram 912.3 MB
EGAF00003249266 cram 864.2 MB
EGAF00003249267 cram 802.4 MB
EGAF00003249268 cram 514.4 MB
EGAF00003249269 cram 848.4 MB
EGAF00003249270 cram 642.7 MB
EGAF00003249271 cram 683.3 MB
EGAF00003249272 cram 695.3 MB
EGAF00003249273 cram 786.3 MB
EGAF00003249274 cram 816.8 MB
EGAF00003249275 cram 762.3 MB
EGAF00003249276 cram 930.2 MB
EGAF00003249277 cram 1.0 GB
EGAF00003249278 cram 787.8 MB
EGAF00003249279 cram 776.3 MB
EGAF00003249280 cram 913.7 MB
EGAF00003249281 cram 866.8 MB
EGAF00003249282 cram 803.5 MB
EGAF00003249283 cram 515.3 MB
EGAF00003249284 cram 851.0 MB
EGAF00003249285 cram 643.4 MB
EGAF00003249286 cram 684.6 MB
EGAF00003249287 cram 696.9 MB
60 Files (47.0 GB)