title: Human Xenobiotic Nuclear Receptor PXR Augments Mycobacterium tuberculosis Survival.
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.
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Ella
authors.initials: E
authors.lastname: Bhagyaraj
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Ravikanth
authors.identifier: 0000-0002-0031-2333
authors.initials: R
authors.lastname: Nanduri
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Ankita
authors.initials: A
authors.lastname: Saini
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Hedwin Kitdorlang
authors.identifier: 0000-0002-8068-4160
authors.initials: HK
authors.lastname: Dkhar
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Nancy
authors.initials: N
authors.lastname: Ahuja
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Vemika
authors.initials: V
authors.lastname: Chandra
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Sahil
authors.initials: S
authors.lastname: Mahajan
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Rashi
authors.initials: R
authors.lastname: Kalra
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Drishti
authors.initials: D
authors.lastname: Tiwari
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and.
authors.forename: Charu
authors.initials: C
authors.lastname: Sharma
authors.affiliation: Government Medical College and Hospital, Chandigarh 160030, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Janmeja
authors.affiliation: Council for Scientific and Industrial Research, Institute of Microbial Technology, Chandigarh 160036, India; and pawan@imtech.res.in.
authors.forename: Pawan
authors.initials: P
authors.lastname: Gupta
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010588:Phagosomes; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D014376:Tuberculosis / Q000276:immunology*; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D015262:Xenobiotics