The within-host dynamics of African trypanosome infections

Matthews, K. R., McCulloch, R. and Morrison, L. J. (2015) The within-host dynamics of African trypanosome infections. Philosophical Transactions of the Royal Society B: Biological Sciences, 370(1675), 20140288. (doi:10.1098/rstb.2014.0288) (PMID:26150654) (PMCID:PMC4528486)

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Abstract

African trypanosomes are single-celled protozoan parasites that are capable of long-term survival while living extracellularly in the bloodstream and tissues of mammalian hosts. Prolonged infections are possible because trypanosomes undergo antigenic variation—the expression of a large repertoire of antigenically distinct surface coats, which allows the parasite population to evade antibody-mediated elimination. The mechanisms by which antigen genes become activated influence their order of expression, most likely by influencing the frequency of productive antigen switching, which in turn is likely to contribute to infection chronicity. Superimposed upon antigen switching as a contributor to trypanosome infection dynamics is the density-dependent production of cell-cycle arrested parasite transmission stages, which limit the infection while ensuring parasite spread to new hosts via the bite of blood-feeding tsetse flies. Neither antigen switching nor developmental progression to transmission stages is driven by the host. However, the host can contribute to the infection dynamic through the selection of distinct antigen types, the influence of genetic susceptibility or trypanotolerance and the potential influence of host-dependent effects on parasite virulence, development of transmission stages and pathogenicity. In a zoonotic infection cycle where trypanosomes circulate within a range of host animal populations, and in some cases humans, there is considerable scope for a complex interplay between parasite immune evasion, transmission potential and host factors to govern the profile and outcome of infection.

Item Type:Articles
Additional Information:Work in K.R.M.'s laboratory is funded by the Wellcome Trust (WT088293, WT103740) and is based in the Centre for Immunity, Infection and Evolution, which is supported by the Wellcome Trust (WT095831). K.M. is a Wellcome Trust Senior Investigator. R.M.'s laboratory is supported by the Wellcome Trust (WT089172) and the BBSRC (BB/M028909/1). The Wellcome Trust Centre for Molecular Parasitology is supported by the Wellcome Trust (085349, 104111). L.J.M. is a Royal Society University Research Fellow (UF090083), and work in his laboratory is supported by the BBSRC (BB/L019035/1) and the Bill & Melinda Gates Foundation (OPP1108042). The Roslin Institute is core-funded by the BBSRC.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McCulloch, Professor Richard
Authors: Matthews, K. R., McCulloch, R., and Morrison, L. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Philosophical Transactions of the Royal Society B: Biological Sciences
Publisher:The Royal Society
ISSN:0962-8436
ISSN (Online):1471-2970
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Philosophical Transactions of the Royal Society B: Biological Sciences 370(1675):20140288
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
160775The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)085349/Z/08/ZIII - Parasitology
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZRIII - Parasitology