The level of H 2 O 2 type oxidative stress regulates virulence of Theileria-transformed leukocytes

Abstract : Theileria annulata infects predominantly macro-phages, and to a lesser extent B cells, and causes a widespread disease of cattle called tropical theileriosis. Disease-causing infected macro-phages are aggressively invasive, but this viru-lence trait can be attenuated by long-term culture. Attenuated macrophages are used as live vaccines against tropical theileriosis and via their charac-terization one gains insights into what host cell trait is altered concomitant with loss of virulence. We established that sporozoite infection of mono-cytes rapidly induces hif1-α transcription and that constitutive induction of HIF-1α in transformed leukocytes is parasite-dependent. In both infected macrophages and B cells induction of HIF-1α acti-vates transcription of its target genes that drive host cells to perform Warburg-like glycolysis. We propose that Theileria-infected leukocytes main-tain a HIF-1α-driven transcriptional programme typical of Warburg glycolysis in order to reduce as much as possible host cell H 2O2 type oxidative stress. However, in attenuated macrophages H2O2 production increases and HIF-1α levels conse-quently remained high, even though adhesion and aggressive invasiveness diminished. This indicates that Theileria infection generates a host leukocytes hypoxic response that if not properly controlled leads to loss of virulence.
Type de document :
Article dans une revue
Cellular Microbiology, Wiley, 2013, pp.269-79. 〈10.1111/cmi.12218〉
Liste complète des métadonnées

Littérature citée [36 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01075079
Contributeur : Mireille Bos <>
Soumis le : jeudi 16 octobre 2014 - 15:32:19
Dernière modification le : jeudi 11 janvier 2018 - 06:23:10
Document(s) archivé(s) le : samedi 17 janvier 2015 - 10:46:18

Fichier

cmi12218.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Mehdi Metheni, Nadia Echebli, Marie Chaussepied, Céline Ransy, Christiane Chéreau, et al.. The level of H 2 O 2 type oxidative stress regulates virulence of Theileria-transformed leukocytes. Cellular Microbiology, Wiley, 2013, pp.269-79. 〈10.1111/cmi.12218〉. 〈inserm-01075079〉

Partager

Métriques

Consultations de la notice

82

Téléchargements de fichiers

90