Mycobacterium tuberculosis exploits human interferon γ to stimulate macrophage extracellular trap formation and necrosis

Ka Wing Wong, Williams R. Jacobs

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Human neutrophils form extracellular traps during M. tuberculosis infection, but a similar phenomenon has not been reported in human macrophages. Here we demonstrate that M. tuberculosis induces release of extracellular traps from human macrophages. This process is regulated by elastase activity, previously shown to regulate formation of extracellular traps by neutrophils. Interestingly, formation of extracellular traps by macrophages during M. tuberculosis infection is inducible by interferon γ (IFN-γ). These traps are mainly produced by heavily infected macrophages. Accordingly, IFN-γ is found to stimulate M. tuberculosis aggregation in macrophages. Both IFN-γ-inducible events, extracellular trap formation and mycobacterial aggregation, require the ESX-1 secretion system. In addition, IFN-γ is found to enhance ESX-1-mediated macrophage necrosis. In the absence of ESX-1, IFN-γ does not restore any extracellular trap formation, mycobacterial aggregation, or macrophage necrosis. Thus, initial characterization of macrophage extracellular trap formation due to M. tuberculosis infection led to the uncovering of a novel role for IFN-γ in amplifying multiple effects of the mycobacterial ESX-1.

Original languageEnglish (US)
Pages (from-to)109-119
Number of pages11
JournalJournal of Infectious Diseases
Volume208
Issue number1
DOIs
StatePublished - Jul 1 2013

Fingerprint

Mycobacterium tuberculosis
Interferons
Necrosis
Macrophages
Mycobacterium Infections
Extracellular Traps
Pancreatic Elastase

Keywords

  • ESX-1
  • extracellular traps
  • human macrophages
  • interferon-γ
  • M. tuberculosis
  • necrosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

@article{085b8969b76e4095a0e7560094adae13,
title = "Mycobacterium tuberculosis exploits human interferon γ to stimulate macrophage extracellular trap formation and necrosis",
abstract = "Human neutrophils form extracellular traps during M. tuberculosis infection, but a similar phenomenon has not been reported in human macrophages. Here we demonstrate that M. tuberculosis induces release of extracellular traps from human macrophages. This process is regulated by elastase activity, previously shown to regulate formation of extracellular traps by neutrophils. Interestingly, formation of extracellular traps by macrophages during M. tuberculosis infection is inducible by interferon γ (IFN-γ). These traps are mainly produced by heavily infected macrophages. Accordingly, IFN-γ is found to stimulate M. tuberculosis aggregation in macrophages. Both IFN-γ-inducible events, extracellular trap formation and mycobacterial aggregation, require the ESX-1 secretion system. In addition, IFN-γ is found to enhance ESX-1-mediated macrophage necrosis. In the absence of ESX-1, IFN-γ does not restore any extracellular trap formation, mycobacterial aggregation, or macrophage necrosis. Thus, initial characterization of macrophage extracellular trap formation due to M. tuberculosis infection led to the uncovering of a novel role for IFN-γ in amplifying multiple effects of the mycobacterial ESX-1.",
keywords = "ESX-1, extracellular traps, human macrophages, interferon-γ, M. tuberculosis, necrosis",
author = "Wong, {Ka Wing} and Jacobs, {Williams R.}",
year = "2013",
month = "7",
day = "1",
doi = "10.1093/infdis/jit097",
language = "English (US)",
volume = "208",
pages = "109--119",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Mycobacterium tuberculosis exploits human interferon γ to stimulate macrophage extracellular trap formation and necrosis

AU - Wong, Ka Wing

AU - Jacobs, Williams R.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Human neutrophils form extracellular traps during M. tuberculosis infection, but a similar phenomenon has not been reported in human macrophages. Here we demonstrate that M. tuberculosis induces release of extracellular traps from human macrophages. This process is regulated by elastase activity, previously shown to regulate formation of extracellular traps by neutrophils. Interestingly, formation of extracellular traps by macrophages during M. tuberculosis infection is inducible by interferon γ (IFN-γ). These traps are mainly produced by heavily infected macrophages. Accordingly, IFN-γ is found to stimulate M. tuberculosis aggregation in macrophages. Both IFN-γ-inducible events, extracellular trap formation and mycobacterial aggregation, require the ESX-1 secretion system. In addition, IFN-γ is found to enhance ESX-1-mediated macrophage necrosis. In the absence of ESX-1, IFN-γ does not restore any extracellular trap formation, mycobacterial aggregation, or macrophage necrosis. Thus, initial characterization of macrophage extracellular trap formation due to M. tuberculosis infection led to the uncovering of a novel role for IFN-γ in amplifying multiple effects of the mycobacterial ESX-1.

AB - Human neutrophils form extracellular traps during M. tuberculosis infection, but a similar phenomenon has not been reported in human macrophages. Here we demonstrate that M. tuberculosis induces release of extracellular traps from human macrophages. This process is regulated by elastase activity, previously shown to regulate formation of extracellular traps by neutrophils. Interestingly, formation of extracellular traps by macrophages during M. tuberculosis infection is inducible by interferon γ (IFN-γ). These traps are mainly produced by heavily infected macrophages. Accordingly, IFN-γ is found to stimulate M. tuberculosis aggregation in macrophages. Both IFN-γ-inducible events, extracellular trap formation and mycobacterial aggregation, require the ESX-1 secretion system. In addition, IFN-γ is found to enhance ESX-1-mediated macrophage necrosis. In the absence of ESX-1, IFN-γ does not restore any extracellular trap formation, mycobacterial aggregation, or macrophage necrosis. Thus, initial characterization of macrophage extracellular trap formation due to M. tuberculosis infection led to the uncovering of a novel role for IFN-γ in amplifying multiple effects of the mycobacterial ESX-1.

KW - ESX-1

KW - extracellular traps

KW - human macrophages

KW - interferon-γ

KW - M. tuberculosis

KW - necrosis

UR - http://www.scopus.com/inward/record.url?scp=84878560300&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878560300&partnerID=8YFLogxK

U2 - 10.1093/infdis/jit097

DO - 10.1093/infdis/jit097

M3 - Article

C2 - 23475311

AN - SCOPUS:84878560300

VL - 208

SP - 109

EP - 119

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 1

ER -