Mycobacterium tuberculosis modulates macrophage lipid-sensing nuclear receptors PPARγ and TR4 for survival.

Mahajan, Sahil and Dkhar, H Kitdorlang and Chandra, Vemika and Dave, Sandeep and Nanduri, Ravikanth and Janmeja, Ashok Kumar and Agrewala, J N and Gupta, Pawan (2012) Mycobacterium tuberculosis modulates macrophage lipid-sensing nuclear receptors PPARγ and TR4 for survival. Journal of immunology (Baltimore, Md. : 1950), 188 (11). pp. 5593-603. ISSN 1550-6606

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Abstract

Mycobacterium tuberculosis-macrophage interactions are key to pathogenesis and clearance of these bacteria. Although interactions between M. tuberculosis-associated lipids and TLRs, non-TLRs, and opsonic receptors have been investigated, interactions of these lipids and infected macrophage lipid repertoire with lipid-sensing nuclear receptors expressed in macrophages have not been addressed. In this study, we report that M. tuberculosis-macrophage lipids can interact with host peroxisome proliferator-activated receptor γ and testicular receptor 4 to ensure survival of the pathogen by modulating macrophage function. These two lipid-sensing nuclear receptors create a foamy niche within macrophage by modulating oxidized low-density lipoprotein receptor CD36, phagolysosomal maturation block by induction of IL-10, and a blunted innate response by alternative polarization of the macrophages, which leads to survival of M. tuberculosis. These results also suggest possible heterologous ligands for peroxisome proliferator-activated receptor γ and testicular receptor 4 and are suggestive of adaptive or coevolution of the host and pathogen. Relative mRNA expression levels of these receptors in PBMCs derived from clinical samples convincingly implicate them in tuberculosis susceptibility. These observations expose a novel paradigm in the pathogenesis of M. tuberculosis amenable for pharmacological modulation.

Item Type:	Article
Additional Information:	Copyright of this article belongs to AAI.
Uncontrolled Keywords:	Mycobacterium tuberculosis; Cell Line; Nuclear Receptor Subfamily 4
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	28 Jan 2013 09:57
Last Modified:	07 Jan 2015 04:53
URI:	http://crdd.osdd.net/open/id/eprint/1250

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