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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Both functional LTβ receptor and TNF receptor 2 are required for the development of experimental cerebral malaria
PLoS ONE, Volume 3, No. 7, Article e2608, Year 2008
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Description
Background: TNF-related lymphotoxin α (LTα) is essential for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The pathway involved has been attributed to TNFR2. Here we show a second arm of LTα signaling essential for ECM development through LTβ-R, receptor of LTα1β2 heterotrimer. Methodology/Principal Findings: LTβR deficient mice did not develop the neurological signs seen in PbA induced ECM but died at three weeks with high parasitaemia and severe anemia like LTαβ deficient mice. Resistance of LTαβ or LTβR deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin+ CD8+ T cells, and their ICAM-1 expression were clearly attenuated in the brain of resistant mice. An essential contribution of LIGHT, another LTβR ligand, could be excluded as LIGHT deficient mice rapidly succumbed to ECM. Conclusions/Significance: LTβR expressed on radioresistant resident stromal, probably endothelial cells, rather than hematopoietic cells, are essential for the development of ECM, as assessed by hematopoietic reconstitution experiment. Therefore, the data suggest that both functional LTβR and TNFR2 signaling are requited and non-redundant for the development of microvascular pathology resulting fatal ECM. © 2008 Togbe et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2442868/bin/pone.0002608.s001.avi
https://efashare.b-cdn.net/share/pmc/articles/PMC2442868/bin/pone.0002608.s002.avi
https://efashare.b-cdn.net/share/pmc/articles/PMC2442868/bin/pone.0002608.s003.avi
https://efashare.b-cdn.net/share/pmc/articles/PMC2442868/bin/pone.0002608.s004.avi
https://efashare.b-cdn.net/share/pmc/articles/PMC2442868/bin/pone.0002608.s005.avi
Authors & Co-Authors
Togbé, Dieudonnée
France, Orleans
Université D'orléans
de Sousa, Paulo Loureiro
France, Orleans
Cbm Centre de Biophysique Moléculaire
Fauconnier, Mathilde
France, Orleans
Université D'orléans
Boissay, Victorine
France, Orleans
Université D'orléans
Fick, Lizette C.E.
South Africa, Cape Town
Institute of Infectious Disease and Molecular Medicine
Scheu, Stefanie
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Pfeffer, Klaus
Germany, Dusseldorf
Heinrich-heine-universität Düsseldorf
Menard, Robert
France, Paris
Institut Pasteur, Paris
Grau, Georges Emile Raymond
Australia, Sydney
The University of Sydney
Doan, Bich Thuy
France, Orleans
Cbm Centre de Biophysique Moléculaire
Beloeil, Jean Claude
France, Orleans
Cbm Centre de Biophysique Moléculaire
RENIA, LAURENT
Australia, Sydney
The University of Sydney
France, Paris
Inserm
Hansen, Anna M.
Australia, Sydney
The University of Sydney
Ball, Helen J.
Australia, Sydney
The University of Sydney
Hunt, Nicholas H.
Australia, Sydney
The University of Sydney
Ryffel, Bernhard
France, Orleans
Université D'orléans
Quesniaux, Valérie F.J.
France, Orleans
Université D'orléans
Statistics
Citations: 49
Authors: 17
Affiliations: 7
Identifiers
Doi:
10.1371/journal.pone.0002608
e-ISSN:
19326203
Research Areas
Infectious Diseases
Study Approach
Quantitative