Related Experiment Video
Updated: Jun 4, 2026
10:10
A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection
Published on: October 5, 2015
NETosis associates with human TB lung tissue destruction and disease pathogenesis
Kimone L Fisher1,2, Thabo Mpotje1, Kievershen Nargan1
1Africa Health Research Institute, KwaZulu-Natal, South Africa.
EMBO Molecular Medicine
|June 2, 2026
Summary
Neutrophil extracellular traps (NETs) contribute to lung damage in tuberculosis (TB). Key drivers of this cell death, like myeloperoxidase (MPO), were identified as potential targets for host-directed therapies (HDT) to reduce lung pathology.
Area of Science:
- Immunology
- Pathology
- Molecular Biology
Background:
- Tuberculosis (TB) lung damage mechanisms are not fully understood.
- NETosis, a form of neutrophil cell death releasing neutrophil extracellular traps (NETs), is implicated but its role in TB pathogenesis requires clarification.
- Identifying targets for host-directed therapies (HDT) is crucial for managing TB-associated lung damage.
Purpose of the Study:
- To investigate the role of NETosis in TB-associated lung pathological damage.
- To identify key drivers of NETosis in TB granulomas.
- To explore potential therapeutic targets for reducing neutrophil-driven lung damage in TB.
Main Methods:
- Proteomic analysis of human TB lung granuloma samples.
- Immunohistochemistry (IHC) to validate protein and NETosis marker abundance.
- Plasma MPO and IP-10 correlation analysis in TB patients.
- In-vitro drug inhibition assays to assess NETosis drivers.
- RT-qPCR to analyze neutrophil-associated gene expression in blood samples.
- Human standardized antigen challenge model to study NETosis-associated gene induction.
Main Results:
- Proteomics revealed enrichment of neutrophil proteins in necrotic TB granuloma regions.
- IHC confirmed abundance of neutrophil markers (MPO, CYBB, NCF1) and NETosis markers (NE, citrullinated H3) in caseous lesions.
- Elevated MPO protein in TB patient plasma correlated with inflammatory marker IP-10.
- Pharmaceutical inhibition of MPO, NE, and CYBB reduced Mycobacterium tuberculosis-induced NETosis in vitro.
- MPO, NCF1, and NCF2 genes were upregulated in TB patients' blood.
- NETosis-associated genes were induced in a human antigen challenge model.
Conclusions:
- NETosis is associated with lung pathological damage in TB.
- Key drivers of neutrophil cell death in TB, including MPO, have been identified.
- These drivers represent potential targets for host-directed therapies (HDT) aimed at mitigating neutrophil-mediated lung damage in TB.
More Related Videos
07:42A Novel Microdissection Approach to Recovering Mycobacterium tuberculosis Specific Transcripts from Formalin Fixed Paraffin Embedded Lung Granulomas
Published on: June 5, 2014
10:04Analysis of 18FDG PET/CT Imaging as a Tool for Studying Mycobacterium tuberculosis Infection and Treatment in Non-human Primates
Published on: September 5, 2017
Related Concept Videos
01:28Pulmonary Tuberculosis II
Tuberculosis, or TB, is a bacterial infectious disease caused by Mycobacterium tuberculosis. While its primary impact is on the lungs, leading to pulmonary tuberculosis, it can also affect various other organs, a condition referred to as extrapulmonary tuberculosis.
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
Here is a detailed explanation of its pathophysiology:
Transmission: The process begins when a person inhales droplet nuclei containing M. tuberculosis. These are typically released into the air when an individual with pulmonary or...
01:23Tuberculosis
Tuberculosis (TB) remains a significant global health concern, primarily targeting the lungs and spreading through airborne transmission. Infection begins when aerosolized droplet nuclei, expelled by an individual with active TB, are inhaled by another person. These microscopic particles carry Mycobacterium tuberculosis, the causative agent of TB. Upon reaching the alveoli, the bacilli are engulfed by alveolar macrophages. However, due to their specialized lipid-rich cell wall, these pathogens...
01:31Pulmonary Tuberculosis III
Tuberculosis (TB) is a contagious infection primarily affecting the lung parenchyma but which can also affect other body parts. TB can be classified based on disease development, presentation, and the affected anatomical site.
The first classification is based on the development of the disease, and it includes the following categories:
The first classification is based on the development of the disease, and it includes the following categories:
01:29Pulmonary Tuberculosis I
Tuberculosis, often called TB, is a contagious illness primarily caused by Mycobacterium tuberculosis. It mainly affects the lung parenchyma but can also impact other body parts.
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
Causative Organism
The primary infectious agent causing tuberculosis is Mycobacterium tuberculosis, a slow-growing, acid-fast, aerobic rod that exhibits sensitivity to heat and ultraviolet light. Instances of Mycobacterium bovis and Mycobacterium avium contributing to the development of TB infection are rare.
Mode of...
01:26Pulmonary Tuberculosis IV
Tuberculosis, more commonly referred to as TB, is an infectious disease stemming from Mycobacterium tuberculosis. While it primarily impacts the lungs, TB can also affect other body areas. Given its severity and global impact, timely and accurate diagnosis is crucial for controlling its spread and improving patient outcomes.
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...
01:23Cystic Fibrosis: Pathogenesis
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...