Advanced Course in Immunology On Demand Lecture Recordings-Molecular and Cellular Mediators of Inflammation

Video Transcription

Video Summary

The speaker discussed how the innate immune system senses danger and balances inflammation with resolution. He emphasized that immune cells, especially phagocytes, are distributed throughout tissues and respond not only to pathogens but also to tissue damage. He reviewed classic concepts of immune sensing: Janeway’s pathogen-associated molecular patterns (PAMPs) and pattern-recognition receptors (PRRs), as well as Matzinger’s danger model and damage-associated molecular patterns (DAMPs). He also highlighted effector-triggered immunity, where the immune system detects pathogen virulence mechanisms rather than only microbial molecules.<br /><br />The main scientific focus was on oxidized phospholipids, especially oxidized PAPC (OxPAPC), which are generated during inflammatory responses. The lab found that microbial stimulation or infection induces OxPAPC accumulation in blood and tissues, particularly in macrophages and dendritic cells. In models of sepsis, Staph aureus infection, and acute respiratory distress syndrome, neutralizing OxPAPC improved survival.<br /><br />Mechanistically, OxPAPC was shown to bind and inhibit AKT, a key metabolic signaling kinase. This rewires macrophage metabolism and epigenetic regulation, increasing H3K27 trimethylation at the IL-10 locus and suppressing IL-10 production. Because IL-10 is an important anti-inflammatory cytokine, blocking OxPAPC worsened disease, while restoring IL-10 signaling or inhibiting the downstream epigenetic enzyme Ezh2 improved survival.<br /><br />The speaker concluded that host-derived oxidized lipids may act as danger signals that shape immunity during infection and inflammatory disease, potentially representing a form of host-dependent effector-triggered immunity.

Asset Subtitle

Lecture 5: Ivan Zanoni, Harvard Medical School, Boston Children’s Hospital

Molecular and Cellular Mediators of Inflammation

Asset Caption

Ivan Zanoni, Harvard Medical School - Boston Children's Hospital
Molecular and Cellular Regulation of Inflammation

Keywords

innate immune system

inflammation

resolution

phagocytes

PAMPs

PRRs

DAMPs

effector-triggered immunity

oxidized phospholipids

OxPAPC

macrophages

IL-10

Ezh2