Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection

Pelle, K. G. et al. (2015) Transcriptional profiling defines dynamics of parasite tissue sequestration during malaria infection. Genome Medicine, 7(1), 19. (doi:10.1186/s13073-015-0133-7) (PMID:25722744) (PMCID:PMC4342211)

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Abstract

Background

During intra-erythrocytic development, late asexually replicating Plasmodium falciparum parasites sequester from peripheral circulation. This facilitates chronic infection and is linked to severe disease and organ-specific pathology including cerebral and placental malaria. Immature gametocytes - sexual stage precursor cells - likewise disappear from circulation. Recent work has demonstrated that these sexual stage parasites are located in the hematopoietic system of the bone marrow before mature gametocytes are released into the bloodstream to facilitate mosquito transmission. However, as sequestration occurs only in vivo and not during in vitro culture, the mechanisms by which it is regulated and enacted (particularly by the gametocyte stage) remain poorly understood.

Results

We generated the most comprehensive P. falciparum functional gene network to date by integrating global transcriptional data from a large set of asexual and sexual in vitro samples, patient-derived in vivo samples, and a new set of in vitro samples profiling sexual commitment. We defined more than 250 functional modules (clusters) of genes that are co-expressed primarily during the intra-erythrocytic parasite cycle, including 35 during sexual commitment and gametocyte development. Comparing the in vivo and in vitro datasets allowed us, for the first time, to map the time point of asexual parasite sequestration in patients to 22 hours post-invasion, confirming previous in vitro observations on the dynamics of host cell modification and cytoadherence. Moreover, we were able to define the properties of gametocyte sequestration, demonstrating the presence of two circulating gametocyte populations: gametocyte rings between 0 and approximately 30 hours post-invasion and mature gametocytes after around 7 days post-invasion.

Conclusions

This study provides a bioinformatics resource for the functional elucidation of parasite life cycle dynamics and specifically demonstrates the presence of the gametocyte ring stages in circulation, adding significantly to our understanding of the dynamics of gametocyte sequestration in vivo.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marti, Professor Matthias
Authors: Pelle, K. G., Oh, K., Buchholz, K., Narasimhan, V., Joice, R., Milner, D. A., Brancucci, N., Ma, S., Voss, T. S., Ketman, K., Seydel, K. B., Taylor, T. E., Barteneva, N. S., Huttenhower, C., and Marti, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Genome Medicine
Publisher:BioMed Central
ISSN:1756-994X
ISSN (Online):1756-994X
Published Online:27 February 2015
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Genome Medicine 7(1):19
Publisher Policy:Reproduced under a Creative Commons License

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