Genetic manipulation of African trypanosomes as a tool to dissect the immunobiology of infection.

Abstract:

:The variant surface glycoprotein (VSG) coat of African trypanosomes exhibits immunobiological functions distinct from its prominent role as a variant surface antigen. In order to address questions regarding immune stealth effects of VSG switch-variant coats, and the innate immune system activating effects of shed VSG substituents, several groups have genetically modified the ability of trypanosomes to express or release VSG during infection of the mammalian host. The role of mosaic surface coats expressed by VSG switch-variants (VSG double-expressors) in escaping early immune detection, and the role of VSG glycosylphosphatidylinositol (GPI) anchor substituents in regulating host immunity have been revealed, respectively, by stable co-expression of an exogenous VSG gene in trypanosomes expressing an endogenous VSG gene, and by knocking out the genetic locus for GPI-phospholipase C (PLC) that releases VSG from the membrane. Both approaches to genetic modification of African trypanosomes have suggested interesting and unexpected immunobiological effects associated with surface coat molecules.

journal_name

Parasite Immunol

journal_title

Parasite immunology

authors

Mansfield JM,Paulnock DM

doi

10.1111/j.1365-3024.2007.01003.x

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

245-53

issue

4

eissn

0141-9838

issn

1365-3024

pii

PIM1003

journal_volume

30

pub_type

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