Related Experiment Video
Updated: Jan 18, 2026
07:32
Preparation of Mycobacterium Tuberculosis Culture Filtrate to Understand TB Pathogenesis
Published on: March 28, 2025
1.1K
Cathepsin Z is a conserved susceptibility factor underlying tuberculosis severity.
Rachel K Meade1,2, Oyindamola O Adefisayo1, Marco T P Gontijo1
1Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.
Plos Biology
|September 9, 2025
Summary
Tuberculosis severity is linked to the cathepsin Z (CTSZ) gene. CTSZ influences inflammation and bacterial load in mice and humans, highlighting a conserved pathway in TB disease progression.
Area of Science:
- Genetics and Immunology
- Host-Pathogen Interactions
- Animal Models of Disease
Background:
- Tuberculosis (TB) presents diverse clinical outcomes, but existing animal models often fail to capture human variability.
- Genetically diverse mouse models, like the Collaborative Cross panel, offer potential for studying TB disease facets and identifying genetic determinants.
- Previous work mapped a TB susceptibility locus on mouse chromosome 2.
Purpose of the Study:
- To identify the specific gene underlying a previously mapped TB susceptibility locus on mouse chromosome 2.
- To investigate the role of cathepsin Z (Ctsz) in TB pathogenesis and disease severity in both murine models and human populations.
- To explore the conserved CTSZ-CXCL1 axis in mediating TB disease severity.
Main Methods:
- Genetic mapping in Collaborative Cross mice to identify candidate genes for TB susceptibility.
- Functional studies involving Ctsz gene ablation in mice to assess its impact on bacterial burden, inflammation, and survival.
- In vitro experiments with murine macrophages to analyze Ctsz's effect on chemokine production (CXCL1).
- Genetic association studies in a Ugandan cohort to link CTSZ variants with TB disease severity.
- Histopathological examination of human TB granulomas to determine CTSZ localization.
Main Results:
- Cathepsin Z (Ctsz) was identified as a key candidate gene for TB susceptibility.
- Ctsz deficiency in mice resulted in increased bacterial load, heightened pulmonary inflammation, and reduced survival.
- Disruption of Ctsz in macrophages enhanced the production of chemokine (C-X-C motif) ligand 1 (CXCL1).
- Significant associations were found between CTSZ variants and TB disease severity in a human cohort.
- CTSZ was localized to macrophages within human TB granulomas, indicating its presence at the host-pathogen interface.
Conclusions:
- Cathepsin Z plays a critical role in modulating TB disease severity.
- A conserved CTSZ-CXCL1 axis in both mice and humans contributes to TB pathogenesis.
- Understanding the role of CTSZ offers potential therapeutic targets for managing TB disease severity.
Related Concept Videos
01:28Pulmonary Tuberculosis II
1.4K
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...
1.4K
01:29Pulmonary Tuberculosis I
846
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...
846
01:31Pulmonary Tuberculosis III
946
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:
946
01:26Pulmonary Tuberculosis IV
480
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...
480
01:28Pulmonary Tuberculosis V
543
Medical management of tuberculosis (TB) patients involves a comprehensive approach that includes diagnosis, treatment, and monitoring. The specific strategies can vary depending on the type of tuberculosis (latent or active), the patient's overall health status, and other considerations.
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
543
01:23Cystic Fibrosis: Pathogenesis
730
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,...
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,...
730