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Inhibition of the Interferon-γ JAK-STAT1 pathway by Leishmania donovani amastigotes

Matte, Christine; Giroux, Mélanie; Descoteaux, Albert . Inhibition of the Interferon-γ JAK-STAT1 pathway by Leishmania donovani amastigotes In: 8e symposium annuel de parasitologie moléculaire du Québec, 12-13 juin 2008, UQAM.

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Résumé

Interferon (IFN)-γ is a highly potent macrophage activator that plays a crucial role in the control and resolution of microbial infections, stimulating key intracellular responses such as reactive oxygen and nitrogen species production and Major Histocompatibility Complex Class II (MHC II) molecule expression. IFN-g-induced signalling events are predominantly centered on the Janus Kinase (JAK)–Signal Transducer and Activator of Transcription 1 (STAT1) pathway, which consequently represents an ideal target for intracellular pathogens. Leishmania parasites are renowned for their capacity to prevent the activation of antimicrobial responses in macrophages. Recent evidence from our laboratory demonstrates that the amastigote stage of L. donovani prevents IFN-g-induced Class II Transactivator and MHC II expression. However, the underlying mechanism of this inhibition remains elusive. Here, we infected bone marrow-derived macrophages with L. donovani amastigotes prior to IFN-γ stimulation to observe the impact of amastigotes on activation of the JAK-STAT1 pathway. Western Blot analyses showed that L. donovani amastigotes inhibit IFN-γ-induced IRF1 expression, an important transcription factor of this pathway, without affecting upstream phosphorylation of JAK2 or STAT1. Western Blot analysis, EMSA and confocal immunofluorescence microscopy indicated that IFN-γ-induced STAT1 nuclear translocation is partially inhibited in L. donovani amastigote-infected cells. Experiments aiming to determine the mechanism by which L. donovani amastigotes inhibit STAT1 nuclear translocation are currently under way. These studies will provide a more thorough understanding of the mechanisms by which L. donovani interferes with IFN-γ-induced macrophage activation and responses. This project is funded by CIHR.

Type de document: Document issu d'une conférence ou d'un atelier
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 02 mai 2018 19:56
Dernière modification: 02 mai 2018 20:01
URI: http://espace.inrs.ca/id/eprint/7101

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