Related Experiment Video

Updated: Apr 21, 2026

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
06:12

Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum

Published on: May 3, 2024

3.8K

Mycobacterium tuberculosis PE25/PPE41 protein complex induces necrosis in macrophages: Role in virulence and disease

Smanla Tundup1, Krishnaveni Mohareer2, Seyed E Hasnain3

  • 1Department of Microbiology, University of Chicago, Chicago, IL, 60637, USA.

FEBS Open Bio
|November 8, 2014
PubMed

Insights

Mycobacterium tuberculosis PE25/PPE41 protein complexes induce necrotic cell death in macrophages, promoting bacterial spread and virulence. This finding offers new insights into tuberculosis pathogenesis and disease reactivation.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Necrotic cell death is crucial for Mycobacterium tuberculosis (M. tuberculosis) dissemination and virulence.
  • Mechanisms driving M. tuberculosis-induced necrosis and bacterial factors involved remain poorly understood.
  • The PE25/PPE41 protein complex, part of the PE/PPE gene family, co-evolved with pathogenic mycobacteria.

Purpose of the Study:

  • To investigate the role of the M. tuberculosis PE25/PPE41 protein complex in host cell death pathways.
  • To elucidate the specific type of cell death induced by the PE25/PPE41 complex.
  • To understand the contribution of PE25/PPE41 to M. tuberculosis virulence.

Main Methods:

  • Cell culture of macrophages.
  • Treatment with purified PE25/PPE41 protein complex.
  • Assessment of cell viability and death pathways (necrosis vs. apoptosis).
  • Analysis of bacterial virulence factors and secretion systems.

Main Results:

  • The PE25/PPE41 protein complex was found to induce necrosis in macrophages.
  • Apoptosis was not observed as a primary cell death mechanism induced by the complex.
  • The PE25/PPE41 complex is secreted via a Type VII secretion system.

Conclusions:

  • The M. tuberculosis PE25/PPE41 protein complex plays a novel role in inducing macrophage necrosis.
  • This necrosis induction is a key mechanism contributing to M. tuberculosis virulence.
  • The PE25/PPE41 complex may be involved in disease reactivation during tuberculosis infection.
Keywords:
MycobacteriumPE/PEEPE25PPE41Rv2431Tuberculosis

More Related Videos

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages06:52

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages

Published on: May 21, 2018

11.4K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

4.0K

Related Concept Videos

Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
7.5K
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
9.8K
Regulation of Bacterial Virulence01:28

Regulation of Bacterial Virulence

Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...
67
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
8
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
5.7K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.7K