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Cerebral vessel laminins and IFN-gamma y define Trypanosoma brucei brucei penetration of the blood-brain barrier

Masocha, W; Robertson, B; Rottenberg, ME; Mhlanga, J; Sorokin, Lydia LU and Kristensson, K (2004) In Journal of Clinical Investigation 114(5). p.689-694
Abstract
Subspecies of Trypanosoma brucei cause severe brain diseases after penetration of the blood-brain barrier. We investigated whether cytokines that modulate inflammatory cell infiltration into the brain also influence T. brucei neuroinvasion. Migration of a rodent pathogenic T. brucei strain from the cerebral blood vessels into the brain parenchyma was impeded in IFN-gamma(-/-), IFN-gamma receptor(-/-) (IFN-gammaR(-/-)), IL-12p40(-/-), and recombinant activating gene-1(-/-) (RAG-1(-/-)) mice as compared with their WT littermates despite higher levels of parasitemia in the mutant strains. Parasites accumulated in the perivascular compartment, confined between the endothelial and the parenchymal basement membranes, in certain areas of the... (More)
Subspecies of Trypanosoma brucei cause severe brain diseases after penetration of the blood-brain barrier. We investigated whether cytokines that modulate inflammatory cell infiltration into the brain also influence T. brucei neuroinvasion. Migration of a rodent pathogenic T. brucei strain from the cerebral blood vessels into the brain parenchyma was impeded in IFN-gamma(-/-), IFN-gamma receptor(-/-) (IFN-gammaR(-/-)), IL-12p40(-/-), and recombinant activating gene-1(-/-) (RAG-1(-/-)) mice as compared with their WT littermates despite higher levels of parasitemia in the mutant strains. Parasites accumulated in the perivascular compartment, confined between the endothelial and the parenchymal basement membranes, in certain areas of the brains of IFN-gamma(-/-), IFN-gammaR(-/-), and RAG-1(-/-) mice. This accumulation occurred around endothelial basement membranes containing the laminin alpha4 chain, while blood vessels showing robust laminin alpha5 chain immunostaining were not associated with parasite infiltration. The number of CD4(+) and CD8(+) T cells infiltrating the brain parenchyma was also reduced in the IFN-gamma(-/-) and IFN-gammaR(-/-) mice. Our findings suggest that lymphocyte-derived IFN-gamma facilitates trypanosome penetration across cerebral blood vessels and that the site of penetration is determined by the composition of the basement membranes of these vessels. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Investigation
volume
114
issue
5
pages
689 - 694
publisher
The Journal of Clinical Investigation
external identifiers
  • wos:000223703300015
  • pmid:15343387
  • scopus:4944260350
ISSN
0021-9738
DOI
10.1172/JCI200422104.
language
English
LU publication?
yes
id
f82d96e7-59eb-470b-a19e-98caaffa4aa9 (old id 268525)
date added to LUP
2007-10-25 15:41:22
date last changed
2017-11-19 04:10:54
@article{f82d96e7-59eb-470b-a19e-98caaffa4aa9,
  abstract     = {Subspecies of Trypanosoma brucei cause severe brain diseases after penetration of the blood-brain barrier. We investigated whether cytokines that modulate inflammatory cell infiltration into the brain also influence T. brucei neuroinvasion. Migration of a rodent pathogenic T. brucei strain from the cerebral blood vessels into the brain parenchyma was impeded in IFN-gamma(-/-), IFN-gamma receptor(-/-) (IFN-gammaR(-/-)), IL-12p40(-/-), and recombinant activating gene-1(-/-) (RAG-1(-/-)) mice as compared with their WT littermates despite higher levels of parasitemia in the mutant strains. Parasites accumulated in the perivascular compartment, confined between the endothelial and the parenchymal basement membranes, in certain areas of the brains of IFN-gamma(-/-), IFN-gammaR(-/-), and RAG-1(-/-) mice. This accumulation occurred around endothelial basement membranes containing the laminin alpha4 chain, while blood vessels showing robust laminin alpha5 chain immunostaining were not associated with parasite infiltration. The number of CD4(+) and CD8(+) T cells infiltrating the brain parenchyma was also reduced in the IFN-gamma(-/-) and IFN-gammaR(-/-) mice. Our findings suggest that lymphocyte-derived IFN-gamma facilitates trypanosome penetration across cerebral blood vessels and that the site of penetration is determined by the composition of the basement membranes of these vessels.},
  author       = {Masocha, W and Robertson, B and Rottenberg, ME and Mhlanga, J and Sorokin, Lydia and Kristensson, K},
  issn         = {0021-9738},
  language     = {eng},
  number       = {5},
  pages        = {689--694},
  publisher    = {The Journal of Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Cerebral vessel laminins and IFN-gamma y define Trypanosoma brucei brucei penetration of the blood-brain barrier},
  url          = {http://dx.doi.org/10.1172/JCI200422104.},
  volume       = {114},
  year         = {2004},
}