Related Experiment Video

Updated: May 2, 2026

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
06:52

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

Published on: May 21, 2018

10.2K

Cytosolic CTH senses bacterial lipoproteins and drives noncanonical inflammasome activation

Qiannv Liu1,2,3, Chunlei Wang1,2,3, Mengqian Li1,2,3

  • 1Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.

Nature Immunology
|April 30, 2026
PubMed

Insights

Macrophages sense intracellular bacterial lipoproteins using cystathionine γ-lyase (CTH), which triggers inflammasome activation. CTH deficiency impairs immune responses to bacterial infections, highlighting the role of cellular redox in infection resistance.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Pathogen-associated molecules interact with membrane-bound and intracellular receptors.
  • Bacterial lipoproteins are known Toll-like receptor 2 ligands, but cytoplasmic sensing mechanisms remain unclear.

Purpose of the Study:

  • To investigate the cytoplasmic recognition of bacterial lipoproteins by macrophages.
  • To elucidate the role of cystathionine γ-lyase (CTH) in this process and its impact on inflammasome activation and infection resistance.

Main Methods:

  • Utilized macrophages (primary and immortalized) and CTH-deficient models.
  • Analyzed inflammasome activation (caspase-11) and immune responses to bacterial infections (Staphylococcus aureus, Listeria monocytogenes).
  • Investigated the biochemical modification of lipoproteins by CTH and the role of cellular redox environment.

Main Results:

  • Bacterial lipoproteins are recognized and hydrolyzed by cytoplasmic cystathionine γ-lyase (CTH) in macrophages.
  • Hydrolyzed lipoproteins activate the noncanonical inflammasome via caspase-11 cleavage.
  • CTH deficiency abrogates inflammasome activation by intracellular lipoproteins and attenuates host defense against bacterial pathogens.
  • Cellular redox environment influences lipoprotein recognition.

Conclusions:

  • CTH mediates the cytoplasmic recognition and processing of bacterial lipoproteins, leading to inflammasome activation.
  • This pathway is crucial for macrophage immune responses against intracellular bacterial infections.
  • Cellular redox homeostasis is a key regulator of innate immunity against bacterial lipoproteins.

More Related Videos

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

19.4K
Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

2.2K

Related Concept Videos

Formation of Lipopolysaccharides01:19

Formation of Lipopolysaccharides

Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
1.1K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.5K
Protein Transport to the Thylakoids01:22

Protein Transport to the Thylakoids

Thylakoids are membrane-bound sac-like structures within the chloroplast that serve as sites for photosynthesis. Thylakoid lumen contains many electron transport proteins and is enclosed by a thylakoid membrane rich in the light-harvesting complex. Proteins targeted to the thylakoids are transported as precursors and are sorted by the general TOC/TIC import pathway. Once the precursor reaches the stroma, stromal processing peptidases remove their transit signal and expose thylakoid signal...
2.2K
Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
105.4K
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...
3.9K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.8K