Related Experiment Video

Updated: Jul 9, 2025

Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
08:24

Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach

Published on: May 2, 2018

19.6K

Host-derived oxidized phospholipids initiate effector-triggered immunity fostering lethality upon microbial encounter

Marco Di Gioia1, Valentina Poli1, Piao J Tan2

  • 1Harvard Medical School and Boston Children's Hospital, Division of Immunology and Division of Gastroenterology, MA 02115, USA.

Biorxiv : the Preprint Server for Biology
|December 4, 2023
PubMed

Insights

Host-derived oxidized phospholipids (oxPLs) emerge during microbial encounters, triggering excessive inflammation. Blocking oxPLs protects hosts by inhibiting AKT signaling, offering a novel therapeutic strategy against inflammatory diseases.

Area of Science:

  • Immunology
  • Molecular Biology
  • Metabolism

Background:

  • Macrophages utilize pattern recognition receptors and effector-triggered immunity (ETI) to detect pathogens.
  • Tissue damage from infections releases host-derived factors that exacerbate inflammation.
  • The sensing mechanisms and immune impact of these self-derived molecules are not well understood.

Approach:

  • Investigated the role of host-derived oxidized phospholipids (oxPLs) in immune responses to microbial encounters in mice and humans.
  • Examined the effects of oxPL blockade on inflammation and host survival.
  • Elucidated the molecular mechanism involving AKT inhibition and its downstream effects on the methionine cycle and IL-10 expression.

Key Points:

  • Host-derived oxPLs are generated upon microbial encounter in both mice and humans.
  • Blocking oxPLs reduces inflammation and prevents host death without impacting pathogen load.
  • oxPLs inhibit AKT, a key regulator of immunity and metabolism, leading to methionine cycle potentiation and epigenetic dampening of IL-10.

Conclusions:

  • Host-derived inflammatory cues can function as 'self' virulence factors, initiating ETI.
  • Targeting oxPL activity presents a potential therapeutic approach to mitigate excessive inflammation during infections.

More Related Videos

Isolation and Chemical Characterization of Lipid A from Gram-negative Bacteria12:57

Isolation and Chemical Characterization of Lipid A from Gram-negative Bacteria

Published on: September 16, 2013

31.8K
Methods to Study Lipid Alterations in Neutrophils and the Subsequent Formation of Neutrophil Extracellular Traps10:58

Methods to Study Lipid Alterations in Neutrophils and the Subsequent Formation of Neutrophil Extracellular Traps

Published on: March 29, 2017

9.6K

Related Concept Videos

Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
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...
1.4K
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
68.4K
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...
3.8K
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...
1.4K
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
790
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
1.7K