Tumor necrosis factor (TNF) receptor-1 (TNFp55) signal transduction and macrophage-derived soluble TNF are crucial for nitric oxide-mediated Trypanosoma congolense parasite killing. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Infectious Diseases Année : 2007

Tumor necrosis factor (TNF) receptor-1 (TNFp55) signal transduction and macrophage-derived soluble TNF are crucial for nitric oxide-mediated Trypanosoma congolense parasite killing.

Stefan Magez
  • Fonction : Auteur
Magdalena Radwanska
  • Fonction : Auteur
Michael Drennan
  • Fonction : Auteur
Lizette Fick
  • Fonction : Auteur
Toya Nath Baral
  • Fonction : Auteur
Nasiema Allie
  • Fonction : Auteur
Muazzam Jacobs
  • Fonction : Auteur
Sergei Nedospasov
  • Fonction : Auteur
Frank Brombacher
  • Fonction : Auteur
Bernhard Ryffel
  • Fonction : Auteur
  • PersonId : 841831
Patrick de Baetselier
  • Fonction : Auteur

Résumé

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 N(G)-monomethyl-l-arginine blocks the trypanolytic activity of the adherent liver cell population, whereas exogenous interferon- gamma 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.

Domaines

Immunologie

Dates et versions

hal-00318508 , version 1 (04-09-2008)

Identifiants

Citer

Stefan Magez, Magdalena Radwanska, Michael Drennan, Lizette Fick, Toya Nath Baral, et al.. 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, 2007, 196 (6), pp.954-62. ⟨10.1086/520815⟩. ⟨hal-00318508⟩

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