Inhibition of apoptosis by Rv2456c through Nuclear factor-κB extends the survival of Mycobacterium tuberculosis

Kristen L. Jurcic Smith, Sunhee Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8+ T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. tuberculosis and host cell apoptosis, we screened M. tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID). One of these FID mutants, FID19, had a transposon insertion in Rv2456c and is important for survival in host cells. The lack of the protein resulted in enhanced caspase-3 mediated apoptosis, which is probably due to an inability to activate nuclear factor-κB. Additionally, FID19 infection enhanced polyfunctional CD8+ T cells and induced a higher frequency of interferon-γ secreting immune cells in a murine model. Taken together, our data suggest that Rv2456c is important for the survival of H37Rv by subduing the innate and ultimately adaptive immune responses of its host by preventing apoptosis of the infected cell. Better understanding of the host-mycobacterial interactions may be beneficial to develop novel drug targets and engineer more efficacious vaccine strains against tuberculosis.

Original languageEnglish (US)
Pages (from-to)426-436
Number of pages11
JournalInternational Journal of Mycobacteriology
Volume5
Issue number4
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Fingerprint

Mycobacterium tuberculosis
Apoptosis
Tuberculosis
T-Lymphocytes
Proteins
Adaptive Immunity
Caspase 3
Interferon-gamma
Immune System
Cell Death
Vaccines
Infection
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Mycobacterium tuberculosis
  • Tuberculosis
  • Vaccine

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Inhibition of apoptosis by Rv2456c through Nuclear factor-κB extends the survival of Mycobacterium tuberculosis. / Jurcic Smith, Kristen L.; Lee, Sunhee.

In: International Journal of Mycobacteriology, Vol. 5, No. 4, 01.12.2016, p. 426-436.

Research output: Contribution to journalArticle

@article{4f37278d24c84410be1120e98c6eba4e,
title = "Inhibition of apoptosis by Rv2456c through Nuclear factor-κB extends the survival of Mycobacterium tuberculosis",
abstract = "Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8+ T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. tuberculosis and host cell apoptosis, we screened M. tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID). One of these FID mutants, FID19, had a transposon insertion in Rv2456c and is important for survival in host cells. The lack of the protein resulted in enhanced caspase-3 mediated apoptosis, which is probably due to an inability to activate nuclear factor-κB. Additionally, FID19 infection enhanced polyfunctional CD8+ T cells and induced a higher frequency of interferon-γ secreting immune cells in a murine model. Taken together, our data suggest that Rv2456c is important for the survival of H37Rv by subduing the innate and ultimately adaptive immune responses of its host by preventing apoptosis of the infected cell. Better understanding of the host-mycobacterial interactions may be beneficial to develop novel drug targets and engineer more efficacious vaccine strains against tuberculosis.",
keywords = "Apoptosis, Mycobacterium tuberculosis, Tuberculosis, Vaccine",
author = "{Jurcic Smith}, {Kristen L.} and Sunhee Lee",
year = "2016",
month = "12",
day = "1",
doi = "10.1016/j.ijmyco.2016.06.018",
language = "English (US)",
volume = "5",
pages = "426--436",
journal = "International Journal of Mycobacteriology",
issn = "2212-5531",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Inhibition of apoptosis by Rv2456c through Nuclear factor-κB extends the survival of Mycobacterium tuberculosis

AU - Jurcic Smith, Kristen L.

AU - Lee, Sunhee

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8+ T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. tuberculosis and host cell apoptosis, we screened M. tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID). One of these FID mutants, FID19, had a transposon insertion in Rv2456c and is important for survival in host cells. The lack of the protein resulted in enhanced caspase-3 mediated apoptosis, which is probably due to an inability to activate nuclear factor-κB. Additionally, FID19 infection enhanced polyfunctional CD8+ T cells and induced a higher frequency of interferon-γ secreting immune cells in a murine model. Taken together, our data suggest that Rv2456c is important for the survival of H37Rv by subduing the innate and ultimately adaptive immune responses of its host by preventing apoptosis of the infected cell. Better understanding of the host-mycobacterial interactions may be beneficial to develop novel drug targets and engineer more efficacious vaccine strains against tuberculosis.

AB - Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8+ T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. tuberculosis and host cell apoptosis, we screened M. tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID). One of these FID mutants, FID19, had a transposon insertion in Rv2456c and is important for survival in host cells. The lack of the protein resulted in enhanced caspase-3 mediated apoptosis, which is probably due to an inability to activate nuclear factor-κB. Additionally, FID19 infection enhanced polyfunctional CD8+ T cells and induced a higher frequency of interferon-γ secreting immune cells in a murine model. Taken together, our data suggest that Rv2456c is important for the survival of H37Rv by subduing the innate and ultimately adaptive immune responses of its host by preventing apoptosis of the infected cell. Better understanding of the host-mycobacterial interactions may be beneficial to develop novel drug targets and engineer more efficacious vaccine strains against tuberculosis.

KW - Apoptosis

KW - Mycobacterium tuberculosis

KW - Tuberculosis

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=84979759262&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979759262&partnerID=8YFLogxK

U2 - 10.1016/j.ijmyco.2016.06.018

DO - 10.1016/j.ijmyco.2016.06.018

M3 - Article

C2 - 27931684

AN - SCOPUS:84979759262

VL - 5

SP - 426

EP - 436

JO - International Journal of Mycobacteriology

JF - International Journal of Mycobacteriology

SN - 2212-5531

IS - 4

ER -