Mce4A protein of Mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a TNF-α dependent manner.
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.
['Saini|Neeraj Kumar|NK|', 'Sinha|Rajesh|R|', 'Singh|Pooja|P|', 'Sharma|Monika|M|', 'Pathak|Rakesh|R|', 'Rathor|Nisha|N|', 'Varma-Basil|Mandira|M|', 'Bose|Mridula|M|']
D017209:Apoptosis D001426:Bacterial Proteins D002460:Cell Line D016207:Cytokines D004926:Escherichia coli D015870:Gene Expression D006801:Humans D057131:Immune Evasion D008264:Macrophages D009169:Mycobacterium tuberculosis D011994:Recombinant Proteins D014409:Tumor Necrosis Factor-alpha
Mce4A Mycobacterium tuberculosis Apoptosis TNF- α