title: Mce4A protein of Mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a TNF-α dependent manner.
abstract: Mycobacterium tuberculosis subverts the host immune response through numerous immune-evasion strategies. Apoptosis has been identified as one such mechanism and has been well studied in M. tuberculosis infection. Here, we demonstrate that the Mce4A protein of mce4 operon is involved in the induction of host cell apoptosis. Earlier we have shown that the Mce4A was required for the invasion and survival of M. tuberculosis. In this report we present evidence to establish a role for Mce4A in the modulation of THP-1 cell survival. Recombinant Mce4A was expressed and purified from Escherichia coli as inclusion bodies and then refolded. Viability of THP-1 cells decreased in a dose-dependent manner when treated with Mce4A. The secretion of pro-inflammatory cytokines like tumor necrosis factor (TNF-α) or interferon gamma (IFN-γ), and enhanced nitric oxide release was observed when the THP-1 cells, were treated with Mce4A protein. The Mce4A induced apoptosis of the THP-1 cells was TNF-α dependent since blocking with anti TNF-α antibody abrogated this phenomenon. Collectively, these data suggest that Mce4A can induce the THP-1 cells to undergo apoptosis which primarily follows a TNF- α dependent pathway.
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: Neeraj Kumar
authors: NK
authors: Saini
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India; Department of Biochemistry, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India.
authors: Rajesh
authors: R
authors: Sinha
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India.
authors: Pooja
authors: P
authors: Singh
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India; Department of Zoology, Miranda House, University of Delhi, Delhi, 110007, India.
authors: Monika
authors: M
authors: Sharma
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India.
authors: Rakesh
authors: R
authors: Pathak
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India.
authors: Nisha
authors: N
authors: Rathor
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India.
authors: Mandira
authors: M
authors: Varma-Basil
authors: Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India. Electronic address: bosemridula@yahoo.co.in.
authors: Mridula
authors: M
authors: Bose
mesh_terms: D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D057131:Immune Evasion; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C510664:Mce4A protein, Mycobacterium tuberculosis; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: Apoptosis; Mce4A; Mycobacterium tuberculosis; TNF- α