Spatially and Genetically Distinct African Trypanosome Virulence Variants Defined by Host Interferon-γ Response

Lorna Mairi MacLean, Martin Odiit, Annette MacLeod, Liam Morrison, Lindsay Sweeney, Anneli Cooper, Peter G. E. Kennedy, Jeremy M Sternberg

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

We describe 2 spatially distinct foci of human African trypansomiasis in eastern Uganda. The Tororo and Soroti foci of Trypanosoma brucei rhodesiense infection were genetically distinct as characterized by 6 microsatellite and 1 minisatellite polymorphic markers and were characterized by differences in disease progression and hostimmune response. In particular, infections with the Tororo genotype exhibited an increased frequency of progression to and severity of the meningoencephalitic stage and higher plasma interferon ( IFN)-gamma concentration, compared with those with the Soroti genotype. We propose that the magnitude of the systemic IFN-gamma response determines the time at which infected individuals develop central nervous system infection and that this is consistent with the recently described role of IFN-gamma in facilitating blood-brain barrier transmigration of trypanosomes in an experimental model of infection. The identification of trypanosome isolates with differing disease progression phenotypes provides the first field-based genetic evidence for virulence variants in T. brucei rhodesiense.

Original languageEnglish
Pages (from-to)1620-1628
Number of pages9
JournalThe journal of infectious diseases
Volume196
Issue number11
DOIs
Publication statusPublished - 1 Dec 2007

Keywords

  • cell proliferative responses
  • brucei-infected mice
  • nitric-oxide
  • sleeping sickness
  • populations
  • suppression
  • resistance
  • IL-10
  • CNS

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