We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria.
- Authors
Togbe, Dieudonnée; de Sousa, Paulo Loureiro; Fauconnier, Mathilde; Boissay, Victorine; Fick, Lizette; Scheu, Stefanie; Pfeffer, Klaus; Menard, Robert; Grau, Georges E.; Doan, Bich-Thuy; Beloeil, Jean Claude; Renia, Laurent; Hansen, Anna M.; Ball, Helen J.; Hunt, Nicholas H.; Ryffel, Bernhard; Quesniaux, Valerie F. J.
- Abstract
Background: TNF-related lymphotoxin a (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 LTbR 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 LTbR and TNFR2 signaling are required and non-redundant for the development of microvascular pathology resulting in fatal ECM.
- Subjects
CEREBRAL malaria; TUMOR necrosis factor receptors; TRANSMISSION of parasitic diseases; BLOOD parasites; ANEMIA; ISCHEMIA; MAGNETIC resonance imaging; ANGIOGRAPHY; MICROCIRCULATION disorders
- Publication
PLoS ONE, 2008, Vol 3, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0002608