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Activation of Endocytosis as an Adaptation to the Mammalian Host by Trypanosomes ^,

The Molteno Building, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, United Kingdom,¹ School of Biological Sciences, University of Bristol, Bristol BS8 1UG, United Kingdom,² Institute of Infection and Immunology Research, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, United Kingdom³

Received 20 June 2007/ Accepted 14 September 2007

Immune evasion in African trypanosomes is principally mediated by antigenic variation, but rapid internalization of surface-bound immune factors may contribute to survival. Endocytosis is upregulated approximately 10-fold in bloodstream compared to procyclic forms, and surface coat remodeling accompanies transition between these life stages. Here we examined expression of endocytosis markers in tsetse fly stages in vivo and monitored modulation during transition from bloodstream to procyclic forms in vitro. Among bloodstream stages nonproliferative stumpy forms have endocytic activity similar to that seen with rapidly dividing slender forms, while differentiation of stumpy forms to procyclic forms is accompanied by rapid down-regulation of Rab11 and clathrin, suggesting that modulation of endocytic and recycling systems accompanies this differentiation event. Significantly, rapid down-regulation of endocytic markers occurs upon entering the insect midgut and expression of Rab11 and clathrin remains low throughout subsequent development, which suggests that high endocytic activity is not required for remodeling the parasite surface or for survival within the fly. However, salivary gland metacyclic forms dramatically increase expression of clathrin and Rab11, indicating that emergence of mammalian infective forms is coupled to reacquisition of a high-activity endocytic-recycling system. These data suggest that high-level endocytosis in Trypanosoma brucei is an adaptation required for viability in the mammalian host.

Published ahead of print on 28 September 2007.

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