Mce4A protein of Mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a TNF-α dependent manner

Neeraj K. Saini, Rajesh Sinha, Pooja Singh, Monika Sharma, Rakesh Pathak, Nisha Rathor, Mandira Varma-Basil, Mridula Bose

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)43-50
Number of pages8
JournalMicrobial Pathogenesis
Volume100
DOIs
StatePublished - Nov 1 2016

Fingerprint

Tumor Necrosis Factor-alpha
Macrophages
Apoptosis
Cytokines
Tuberculosis
Immune Evasion
Inclusion Bodies
Operon
Mycobacterium tuberculosis
Interferon-gamma
Nitric Oxide
Proteins
Escherichia coli
Mycobacterium tuberculosis Mce4A protein
Antibodies
Infection

Keywords

  • Apoptosis
  • Mce4A
  • Mycobacterium tuberculosis
  • TNF- α

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

Cite this

Mce4A protein of Mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a TNF-α dependent manner. / Saini, Neeraj K.; Sinha, Rajesh; Singh, Pooja; Sharma, Monika; Pathak, Rakesh; Rathor, Nisha; Varma-Basil, Mandira; Bose, Mridula.

In: Microbial Pathogenesis, Vol. 100, 01.11.2016, p. 43-50.

Research output: Contribution to journalArticle

Saini, Neeraj K. ; Sinha, Rajesh ; Singh, Pooja ; Sharma, Monika ; Pathak, Rakesh ; Rathor, Nisha ; Varma-Basil, Mandira ; Bose, Mridula. / Mce4A protein of Mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a TNF-α dependent manner. In: Microbial Pathogenesis. 2016 ; Vol. 100. pp. 43-50.
@article{6c824ee97e9b4a2cbb6617a9a2386455,
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.",
keywords = "Apoptosis, Mce4A, Mycobacterium tuberculosis, TNF- α",
author = "Saini, {Neeraj K.} and Rajesh Sinha and Pooja Singh and Monika Sharma and Rakesh Pathak and Nisha Rathor and Mandira Varma-Basil and Mridula Bose",
year = "2016",
month = "11",
day = "1",
doi = "10.1016/j.micpath.2016.08.038",
language = "English (US)",
volume = "100",
pages = "43--50",
journal = "Microbial Pathogenesis",
issn = "0882-4010",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Mce4A protein of Mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a TNF-α dependent manner

AU - Saini, Neeraj K.

AU - Sinha, Rajesh

AU - Singh, Pooja

AU - Sharma, Monika

AU - Pathak, Rakesh

AU - Rathor, Nisha

AU - Varma-Basil, Mandira

AU - Bose, Mridula

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Mce4A

KW - Mycobacterium tuberculosis

KW - TNF- α

UR - http://www.scopus.com/inward/record.url?scp=84986631520&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84986631520&partnerID=8YFLogxK

U2 - 10.1016/j.micpath.2016.08.038

DO - 10.1016/j.micpath.2016.08.038

M3 - Article

C2 - 27592091

AN - SCOPUS:84986631520

VL - 100

SP - 43

EP - 50

JO - Microbial Pathogenesis

JF - Microbial Pathogenesis

SN - 0882-4010

ER -