The 19 kDa Mycobacterium tuberculosis Lipoprotein LpqH Induces Macrophage Apoptosis through Extrinsic and Intrinsic Pathways: A Role for the Mitochondrial Apoptosis-Inducing FactorReport as inadecuate




The 19 kDa Mycobacterium tuberculosis Lipoprotein LpqH Induces Macrophage Apoptosis through Extrinsic and Intrinsic Pathways: A Role for the Mitochondrial Apoptosis-Inducing Factor - Download this document for free, or read online. Document in PDF available to download.

Clinical and Developmental ImmunologyVolume 2012 2012, Article ID 950503, 11 pages

Research ArticleDepartamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Circuito Escolar S-N, Ciudad Universitaria, 04510 México, DF, Mexico

Received 17 September 2012; Revised 7 November 2012; Accepted 20 November 2012

Academic Editor: Maciej Cedzynski

Copyright © 2012 Alejandro Sánchez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We describe the association of caspase-dependent and caspase-independent mechanisms in macrophage apoptosis induced by LpqH, a 19 kDa Mycobacterium tuberculosis lipoprotein. LpqH triggered TLR2 activation, with upregulation of death receptors and ligands, which was followed by a death receptor signaling cascade with activation of initiator caspase 8 and executioner caspase 3. In this caspase-mediated phase, mitochondrial factors were involved in loss of mitochondrial transmembrane potential , release of cytochrome c, and caspase 9 activation. Interestingly, a caspase-independent pathway was also identified; by immunoblot, the mitochondrial apoptosis inducing factor AIF was demonstrated in nuclei and cytosol of LpqH-treated macrophages. Confocal microscopy revealed translocation of AIF to the nuclei of the majority of apoptotic cells. These findings emphasize the complex and redundant nature of the macrophage death response to mycobacteria.





Author: Alejandro Sánchez, Patricia Espinosa, Teresa García, and Raúl Mancilla

Source: https://www.hindawi.com/



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