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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Tumor necrosis factor (TNF) receptor-1 (TNFp55) signal transduction and macrophage-derived soluble TNF are crucial for nitric oxide-mediated Trypanosoma congolense parasite killing
Journal of Infectious Diseases, Volume 196, No. 6, Year 2007
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Description
Control of Trypanosoma congolense infections requires an early cell-mediated immune response. To unravel the role of tumor necrosis factor (TNF) in this process, 6 different T. congolense strains were used in 6 different gene-deficient mouse models that included TNF-/-, TNF receptor-1 (TNFp55)-/-, and TNF receptor-2 (TNFp75)-/- mice, 2 cell type-specific TNF-/- mice, as well as TNF-knock-in mice that expressed only membrane-bound TNF. Our results indicate that soluble TNF produced by macrophages/neutrophils and TNFp55 signaling are essential and sufficient to control parasitemia. The downstream mechanism in the control of T. congolense infection depends on inducible nitric oxide synthase activation in the liver. Such a role for nitric oxide is corroborated ex vivo, because the inhibitor NG-monomethyl-L-arginine blocks the trypanolytic activity of the adherent liver cell population, whereas exogenous interferon-γ that stimulates nitric oxide production enhances parasite killing. In conclusion, the control of T. congolense infection depends on macrophage/neutrophil-derived soluble TNF and intact TNFp55 signaling, which induces trypanolytic nitric oxide. © 2007 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Magez, Stefan
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Belgium, Brussels
Vrije Universiteit Brussel
South Africa, Cape Town
University of Cape Town
Radwanska, Magdalena
Belgium, Brussels
Université Libre de Bruxelles
South Africa, Cape Town
University of Cape Town
Drennan, Michael B.
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Belgium, Brussels
Vrije Universiteit Brussel
South Africa, Cape Town
University of Cape Town
Fick, Lizette C.E.
South Africa, Cape Town
University of Cape Town
Baral, Toya Nath
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Belgium, Brussels
Vrije Universiteit Brussel
Allie, Nasiema
South Africa, Cape Town
University of Cape Town
Jacobs, Muazzam
South Africa, Cape Town
University of Cape Town
Nedospasov, Sergei A.
Russian Federation, Moscow
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Brombacher, Frank
South Africa, Cape Town
University of Cape Town
Ryffel, Bernhard
South Africa, Cape Town
University of Cape Town
France, Orleans
Immunologie et Neurogénétique Expérimentales et Moléculaire Inem
de Baetseĺier, Patrick C.
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Belgium, Brussels
Vrije Universiteit Brussel
Statistics
Citations: 60
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1086/520815
ISSN:
00221899
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study