Cerebral vessel laminins and IFN-gamma y define Trypanosoma brucei brucei penetration of the blood-brain barrier
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/268525
- author
- Masocha, W ; Robertson, B ; Rottenberg, ME ; Mhlanga, J ; Sorokin, Lydia LU and Kristensson, K
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Clinical Investigation
- volume
- 114
- issue
- 5
- pages
- 689 - 694
- publisher
- The American Society for Clinical Investigation
- external identifiers
-
- wos:000223703300015
- pmid:15343387
- scopus:85047690580
- ISSN
- 0021-9738
- DOI
- 10.1172/JCI200422104.
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000)
- id
- f82d96e7-59eb-470b-a19e-98caaffa4aa9 (old id 268525)
- date added to LUP
- 2016-04-01 16:30:53
- date last changed
- 2022-03-15 01:01:36
@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 American Society for 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.}},
doi = {{10.1172/JCI200422104.}},
volume = {{114}},
year = {{2004}},
}