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

Abstract

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.

Evolutionary reconstruction of the retromer complex and its function in Trypanosoma brucei

“…As an excavate, T. brucei is distantly related to mammals and yeast but possesses a well-characterised endomembrane system (Field and Carrington, 2009). T. brucei Vps5 mRNA expression (Tb09.211.4240) is strongly upregulated in the mammalian form (Koumandou et al, 2008) where endocytosis is also upregulated (Natesan et al, 2007); this is consistent with a role for T. brucei Vps5 in endocytic activity.…”

Ubiquitylation and Developmental Regulation of Invariant Surface Protein Expression in Trypanosomes

“…Developmental modulation of mRNA levels in trypanosomes requires many factors and certainly correlates only approximately with corresponding protein levels. For example, Rab11 mRNA abundance is similar in BSFs and PCFs but much higher at the protein level in BSFs (27). However, these data indicate that ISG75 mRNA is made to appreciable quantities in PCFs, albeit much less than in BSFs.…”

Cellular and Molecular Remodeling of the Endocytic Pathway during Differentiation of Trypanosoma brucei Bloodstream Forms

“…Therefore, in contrast with the marked differences distinguishing bloodstream and insect-specific procyclic forms (PFs), SL and ST forms share most endocytic characteristics (20). For instance, high Tf and membrane uptake rates were shown to be maintained and even increased in ST forms (7,20). However, the ability to divide clearly distinguishes these developmental forms, and this difference might result in different requirements for nutrients.…”

“…SL and ST forms are exposed to the same environmental challenges in terms of immune escape and antibody clearance. Therefore, in contrast with the marked differences distinguishing bloodstream and insect-specific procyclic forms (PFs), SL and ST forms share most endocytic characteristics (20). For instance, high Tf and membrane uptake rates were shown to be maintained and even increased in ST forms (7,20).…”