The Cytological Events and Molecular Control of Life Cycle Development of Trypanosoma brucei in the Mammalian Bloodstream

Eleanor Silvester,Keith Matthews,Kirsty McWilliam

doi:10.3390/pathogens6030029

Eleanor Silvester, Keith Matthews + Show 1 more

Open Access

https://doi.org/10.3390/pathogens6030029

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Abstract

African trypanosomes cause devastating disease in sub-Saharan Africa in humans and livestock. The parasite lives extracellularly within the bloodstream of mammalian hosts and is transmitted by blood-feeding tsetse flies. In the blood, trypanosomes exhibit two developmental forms: the slender form and the stumpy form. The slender form proliferates in the bloodstream, establishes the parasite numbers and avoids host immunity through antigenic variation. The stumpy form, in contrast, is non-proliferative and is adapted for transmission. Here, we overview the features of slender and stumpy form parasites in terms of their cytological and molecular characteristics and discuss how these contribute to their distinct biological functions. Thereafter, we describe the technical developments that have enabled recent discoveries that uncover how the slender to stumpy transition is enacted in molecular terms. Finally, we highlight new understanding of how control of the balance between slender and stumpy form parasites interfaces with other components of the infection dynamic of trypanosomes in their mammalian hosts. This interplay between the host environment and the parasite’s developmental biology may expose new vulnerabilities to therapeutic attack or reveal where drug control may be thwarted by the biological complexity of the parasite’s lifestyle.

Highlights

Persistence in regularly changing environments demands that vector-transmitted pathogens rapidly adapt to fluctuating conditions
The development of T. brucei in the mammalian host is likely coordinated through a complex network of interactions with quorum-sensing mediated density control modulated by different host environments whether this be different host species or different compartments within one host
In field settings, the chronic nature of African trypanosome infections often results in co-infections between T. brucei and the other African trypanosome species, Trypanosoma congolense and Trypanosoma vivax [116,117,118]

Summary

Introduction

Persistence in regularly changing environments demands that vector-transmitted pathogens rapidly adapt to fluctuating conditions. Tsetse a particular challenge in that it to must in the bloodstream be transmitted, but midgut to differentiate the survive life long cycle enough stage and establish infection. On uptake to the parasites must evade immune ensure parasite survival andavailability avoid excessive exploitation of tsetse fly midgut (orange attack section),to the parasites face a shift in nutrient and temperature host resources ensure the host enough toestablishment enable successful to the tsetse amongtoother challenges. For example, the parasite must face a host immune response that is switching, of their expressed Variant Surface Glycoprotein (VSG) coat, a process termed antigenic constantlyvariation trying to[2].control the infection. We reflect on outstanding questions relating to T. brucei differentiation and infection dynamics in the mammalian host

Characterisation of Slender and Stumpy Cells

Tools to Understand Life Cycle Development

Molecular Components of the Slender to Stumpy Regulatory Pathway

Future Considerations

Conclusions