Critical interplay between parasite differentiation, host immunity and antigenic variation in trypanosome infections

Gjini, E., Haydon, D. , Barry, J. and Cobbold, C. (2010) Critical interplay between parasite differentiation, host immunity and antigenic variation in trypanosome infections. American Naturalist, 176(4), pp. 424-439. (doi: 10.1086/656276)

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Abstract

Increasing availability of pathogen genomic data offers new opportunities to understand the fundamental mechanisms of immune evasion and pathogen population dynamics during chronic infection. Motivated by the growing knowledge on the antigenic variation system of the sleeping sickness parasite, the African trypanosome, we introduce a mechanistic framework for modeling within‐host infection dynamics. Our analysis focuses first on a single parasitemia peak and then on the dynamics of multiple peaks that rely on stochastic switching between groups of parasite variants. A major feature of trypanosome infections is the interaction between variant‐specific host immunity and density‐dependent parasite differentiation to transmission life stages. In this study, we investigate how the interplay between these two types of control depends on the modular structure of the parasite antigenic archive. Our model shows that the degree of synchronization in stochastic variant emergence determines the relative dominance of general over specific control within a single peak. A requirement for multiple‐peak dynamics is a critical switch rate between blocks of antigenic variants, which implies constraints on variant surface glycoprotein (VSG) archive genetic diversification. Our study illustrates the importance of quantifying the links between parasite genetics and within‐host dynamics and provides insights into the evolution of trypanosomes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cobbold, Professor Christina and Haydon, Professor Daniel and Gjini, Ms Erida and Barry, Professor J
Authors: Gjini, E., Haydon, D., Barry, J., and Cobbold, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Science and Engineering > School of Mathematics and Statistics > Mathematics
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:American Naturalist
Publisher:University of Chicago Press
ISSN:0003-0147

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