Related Experiment Video
Updated: Sep 21, 2025
Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF1
Published on: February 28, 2025
Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium
Lucero A Ramon-Luing1, Yessica Olvera2, Julio Flores-Gonzalez1
1Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas", Mexico City 14080, Mexico.
Abstract:
Macrophages are necessary to eliminate pathogens. However, some pathogens have developed mechanisms to avoid the immune response. One of them is modulating the cell death mechanism to favor pathogen survival. In this study, we evaluated if virulent Mycobacterium tuberculosis (M. tb) can simultaneously activate more than one cell death mechanism. We infected human monocyte-derived macrophages (MDM) in vitro with avirulent (H37Ra) and virulent (H37Rv) strains, and then we measured molecules involved in apoptosis, necroptosis, and pyroptosis. Our data showed that H37Rv infection increased the BCL-2 transcript and protein, decreased the BAX transcript, and increased phosphorylated BCL-2 at the protein level. Moreover, H37Rv infection increased the expression of the molecules involved in the necroptotic pathway, such as ASK1, p-38, RIPK1, RIPK3, and caspase-8, while H37Ra increased caspase-8 and decreased RIPK3 at the transcriptional level. In addition, NLRP3 and CASP1 expression was increased at low MOI in both strains, while IL-1β was independent of virulence but dependent on infection MOI, suggesting the activation of pyroptosis. These findings suggest that virulent M. tb inhibits the apoptosis mediated by BCL-2 family molecules but, at the same time, increases the expression of molecules involved in apoptosis, necroptosis, and pyroptosis at the transcriptional and protein levels, probably as a mechanism to avoid the immune response and guarantee its survival.
Insights
Virulent Mycobacterium tuberculosis (M. tb) manipulates macrophage cell death pathways, inhibiting apoptosis while activating necroptosis and pyroptosis. This complex immune evasion strategy ensures pathogen survival.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Macrophages are crucial for pathogen clearance.
- Pathogens like Mycobacterium tuberculosis (M. tb) evade immune responses by manipulating host cell death.
- Understanding M. tb's impact on apoptosis, necroptosis, and pyroptosis is vital.
Purpose of the Study:
- To investigate if virulent M. tb simultaneously activates multiple macrophage cell death pathways.
- To compare the effects of virulent (H37Rv) and avirulent (H37Ra) M. tb strains on host cell death mechanisms.
Main Methods:
- In vitro infection of human monocyte-derived macrophages (MDM) with M. tb strains.
- Quantification of molecules involved in apoptosis, necroptosis, and pyroptosis pathways.
- Analysis of transcript and protein levels of key cell death regulators.
Main Results:
- Virulent H37Rv modulated BCL-2 family molecules, inhibiting apoptosis while upregulating necroptosis markers (ASK1, RIPK1, RIPK3, caspase-8).
- Both H37Rv and H37Ra increased pyroptosis markers (NLRP3, CASP1) at low multiplicities of infection (MOI).
- Virulent M. tb appears to inhibit apoptosis while promoting necroptosis and pyroptosis, suggesting a multi-pronged immune evasion strategy.
Conclusions:
- Virulent M. tb actively suppresses apoptosis via BCL-2 family modulation.
- M. tb simultaneously upregulates transcriptional and protein expression of apoptosis, necroptosis, and pyroptosis molecules.
- These combined cell death pathway modulations likely facilitate M. tb survival and immune evasion.
More Related Videos
06:49Visualization of Macrophage Lytic Cell Death During Mycobacterial Infection in Zebrafish Embryos via Intravital Microscopy
Published on: January 9, 2019
10:43Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
Related Concept Videos
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:28Pulmonary Tuberculosis II
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...
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
01:17Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
01:17The Extrinsic Apoptotic Pathway
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...