Human Xenobiotic Nuclear Receptor PXR Augments Mycobacterium tuberculosis Survival.

Bhagyaraj, Ella and Nanduri, Ravikanth and Saini, Ankita and Dkhar, Hedwin Kitdorlang and Ahuja, Nancy and Chandra, Vemika and Mahajan, Sahil and Kalra, Rashi and Tiwari, Drishti and Sharma, Charu and Janmeja, Ashok Kumar and Gupta, Pawan (2016) Human Xenobiotic Nuclear Receptor PXR Augments Mycobacterium tuberculosis Survival. Journal of immunology , 197 (1). pp. 244-55. ISSN 1550-6606

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Abstract

Mycobacterium tuberculosis can evade host defense processes, thereby ensuring its survival and pathogenesis. In this study, we investigated the role of nuclear receptor, pregnane X receptor (PXR), in M. tuberculosis infection in human monocyte-derived macrophages. In this study, we demonstrate that PXR augments M. tuberculosis survival inside the host macrophages by promoting the foamy macrophage formation and abrogating phagolysosomal fusion, inflammation, and apoptosis. Additionally, M. tuberculosis cell wall lipids, particularly mycolic acids, crosstalk with human PXR (hPXR) by interacting with its promiscuous ligand binding domain. To confirm our in vitro findings and to avoid the reported species barrier in PXR function, we adopted an in vivo mouse model expressing hPXR, wherein expression of hPXR in mice promotes M. tuberculosis survival. Therefore, pharmacological intervention and designing antagonists to hPXR may prove to be a promising adjunct therapy for tuberculosis.

Item Type:	Article
Additional Information:	Copyright of this article belongs to American Association of Immunologists
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	30 Sep 2016 05:16
Last Modified:	30 Sep 2016 05:16
URI:	http://crdd.osdd.net/open/id/eprint/1855

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