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Trypanosomal immune evasion, chronicity and transmission: an elegant balancing act

Nature Reviews Microbiology volume 10, pages 431–438 (2012)Cite this article

Subjects

Key Points

  • African trypanosomes generate chronic infections, extending over months or years, in mammalian hosts.

  • The infection profile of trypanosomes is influenced by their rate of immune evasion by antigenic variation. A further contributor to the infection profile is the rate of differentiation from proliferative slender forms to non-proliferative transmission stages called stumpy forms.

  • Recent mathematical models have demonstrated the importance of stumpy formation for infection chronicity and, together with cytological analyses, have provided a description of the temporal order of events that generate stumpy forms.

  • We propose that the interplay between antigenic variation and parasite development optimizes the ability to establish and be sustained in mammalian hosts in the field.

  • In the tsetse fly vector, trypanosomal commitment to onward differentiation and establishment is governed by a phosphatase signalling cascade that forms a novel bistable switch.

  • We propose that density-sensing mechanisms in the mammalian host are sustained by an evolutionary selection for transmission competence.

Abstract

During their life cycle, trypanosomes must overcome conflicting demands to ensure their survival and transmission. First, they must evade immunity without overwhelming the host. Second, they must generate and maintain transmission stages at sufficient levels to allow passage into their tsetse vector. Finally, they must rapidly commit to onward development when they enter the tsetse fly. On the basis of recent quantification and modelling of Trypanosoma brucei infection dynamics, we propose that the interplay between immune evasion and development achieves both infection chronicity and transmissibility. Moreover, we suggest that a novel form of bistable regulation ensures developmental commitment on entry into the tsetse fly midgut.

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Figure 1: The life cycle and immune evasion of African trypanosomes.
Figure 2: Cytological events that accompany the transition from slender to stumpy forms.
Figure 3: The contribution of slender and stumpy forms to a chronic infection.
Figure 4: TbPTP1–TbPIP39 signalling and bistability.
Figure 5: The impact of defects in stumpy induction factor production or detection on parasite growth and transmission.

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Acknowledgements

The authors are grateful to J. D. Barry for helpful comments on the manuscript and for providing useful additional insight during the preparation of the manuscript. Work in the K.R.M. laboratory is supported by the Wellcome Trust and by a Wellcome Trust Strategic Award to the Centre for Immunity, Infection and Evolution at the University of Edinburgh, UK. Work in the N.J.S. group is supported by the Wellcome Trust (grant number 082601/Z/07/Z).

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  1. Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh, EH9 3JT, United Kingdom

    Paula MacGregor, Balazs Szöőr, Nicholas J. Savill & Keith R. Matthews

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MacGregor, P., Szöőr, B., Savill, N. et al. Trypanosomal immune evasion, chronicity and transmission: an elegant balancing act. Nat Rev Microbiol 10, 431–438 (2012). https://doi.org/10.1038/nrmicro2779

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