Antigenic variation in Trypanosoma brucei: joining the DOTs

Stockdale, C., Swiderski, M. R., Barry, J. D. and McCulloch, R. (2008) Antigenic variation in Trypanosoma brucei: joining the DOTs. PLoS Biology, 6(7), e185. (doi:10.1371/journal.pbio.0060185)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pbio.0060185

Abstract

African trypanosomes, such as <i>Trypanosoma brucei</i>, are protistan parasites that cause sleeping sickness. Though first described more than a century ago, trypanosomes remain a blight on the health of the human population and on the economy of sub-Saharan Africa. <i>T. brucei</i> replicates in the bloodstream of infected mammals and traverses the blood-brain barrier to enter the central nervous system in the late, frequently fatal, stages of the disease. Because of its extracellular lifestyle, <i>T. brucei</i> is continuously exposed to antibody challenge. To circumvent this, the parasite uses antigenic variation of a surface protein named the variant surface glycoprotein (VSG). Around 107 VSG molecules are expressed on the parasite's cell surface, creating a dense coat that prevents adaptive immunity from detecting or accessing invariant antigens. However, antibodies against the expressed VSG are generated, and periodic switches to an immunologically distinct VSG coat are necessary for parasite survival. Such switches are pre-emptive of the immune response and contribute to the pattern of trypanosome growth seen in an infected host (Figure 1): parasite numbers increase, but then drop as VSG-specific antibodies are raised by the host. Cells that have switched to another VSG coat survive this killing and seed the outgrowth of a subsequent peak of parasites, which is again decimated by anti-VSG immune killing. As a survival strategy, antigenic variation succeeds by prolonging the time that the parasite r

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McCulloch, Professor Richard and Stockdale, Dr Christopher and Swiderski, Dr Michal and Barry, Professor Dave
Authors: Stockdale, C., Swiderski, M. R., Barry, J. D., and McCulloch, R.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Biology
Publisher:Public Library of Science
ISSN:1544-9173
ISSN (Online):1545-7885
Copyright Holders:Copyright
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
401101DNA recombination pathways and antigenic variation in trypanosoma bruceiRichard McCullochMedical Research Council (MRC)G0401553Infection Immunity and Inflammation Life Sciences