Apoptosis triggered by Rv1818c, a PE family gene from Mycobacterium tuberculosis is regulated by mitochondrial intermediates in T cells

Balaji, Kithiganahalli N and Goyal, Girija and Narayana, Yeddula and Srinivas, Madduri and Chaturvedi, Rashmi and Mohammad, Saleemulla (2007) Apoptosis triggered by Rv1818c, a PE family gene from Mycobacterium tuberculosis is regulated by mitochondrial intermediates in T cells. In: Microbes and Infection, 9 (3). pp. 271-281.

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Abstract

Ectopic expression of the Mycobacterium tuberculosis PE- family gene Rv1818c, triggers apoptosis in the mammalian Jurkat T cells, which is blocked by anti-apoptotic protein Bcl-2. Although complete overlap is not observed, a considerable proportion of cellular pools of ectopically expressed Rv1818c localizes to mitochondria. However, recombinant Rv1818c does not trigger release of cytochrome c from isolated mitochondria even though Rv1818c protein induced apoptosis of Jurkat T cells. Apoptosis induced by Rv1818c is blocked by the broad-spectrum caspase inhibitory peptide zVAD-FMK. Unexpectedly, Rv1818c-induced apoptosis is not blocked in a Jurkat sub-clone deficient for caspase-8 (JI 9.2) or in cells where caspase-9 function is inhibited or expression of caspase-9 reduced by siRNA, arguing against a central role for these caspases in Rv1818c-induced apoptotic signaling. Depleting cellular pools of the mitochondrial protein Smac/DIABLO substantially reduces apoptosis consistent with mitochondrial involvement in this death pathway. We present evidence that Rv1818c-induced apoptosis is blocked by the co-transfection of an endogenous inhibitor of caspase activation, XIAP in T cells. Additionally, Rv1818c is released into extracellular environment via exosomes secreted by M. tuberculosis infected BM-DC’s and macrophages. Furthermore, the extracellular Rv1818c protein can be detected in T cells co-cultured with infected BM-DC’s. Taken together, these data suggest that Rv1818c-induced apoptotic signaling is likely regulated in part by the Smac-dependent activation of caspases in T cells.

Item Type:	Journal Article
Publication:	Microbes and Infection
Publisher:	Elsevier
Additional Information:	Copyright of this article belongs to Elsevier.
Keywords:	Apoptosis;PE family gene;Tuberculosis
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	06 Aug 2007
Last Modified:	19 Sep 2010 04:38
URI:	http://eprints.iisc.ac.in/id/eprint/11634

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