Ubiquilin 1 Promotes IFN-γ-Induced Xenophagy of

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More people die from Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), than any other bacterial pathogen. It has long been appreciated that Mtb can survive and divide within macrophages, white blood cells that normally kill bacteria. Macrophages are able to partially control Mtb through a degradative process called autophagy. Autophagy is activated by the cytokine interferon-gamma (IFN-γ), which promotes control of Mtb infection. How the tubercle bacilli are targeted to the autophagy pathway remains unclear. Here we show that the human protein ubiquilin 1 can interact with Mtb surface proteins and associate with Mtb that are present in the host cell cytosol. We propose a model in which activating autophagy with IFN-γ promotes UBQLN1 recruitment to Mtb, which in turn leads to recruitment of the autophagy machinery, autophagy-mediated degradation of the bacteria, and activation of effector T cells. Since IFN-γ is critical in human control of Mtb, our study suggests that polymorphisms in ubiquilins, known to influence susceptibility to neurodegenerative illnesses, might also play a role in host defense against Mtb.

Vyšlo v časopise: Ubiquilin 1 Promotes IFN-γ-Induced Xenophagy of. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005076
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005076

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