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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.
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Submitted on : Thursday, October 16, 2014 - 3:32:19 PM
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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⟩



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