Cited by 221Immune Response and InflammationInflammasome and immune disordersPhagocytosis and Immune Regulation

By Capturing Inflammatory Lipids Released from Dying Cells, the Receptor CD14 Induces Inflammasome-Dependent Phagocyte Hyperactivation

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Zanoni, Ivan, Tan, Yunhao, Di Gioia, Marco, Springstead, James R., Kagan, Jonathan C.·2017·Immunity

Abstract

A heterogeneous mixture of lipids called oxPAPC, derived from dying cells, can hyperactivate dendritic cells (DCs) but not macrophages. Hyperactive DCs are defined by their ability to release interleukin-1 (IL-1) while maintaining cell viability, endowing these cells with potent aptitude to stimulate adaptive immunity. Herein, we found that the bacterial lipopolysaccharide receptor CD14 captured extracellular oxPAPC and delivered these lipids into the cell to promote inflammasome-dependent DC hyperactivation. Notably, we identified two specific components within the oxPAPC mixture that hyperactivated macrophages, allowing these cells to release IL-1 for several days, by a CD14-dependent process. In murine models of sepsis, conditions that promoted cell hyperactivation resulted in inflammation but not lethality. Thus, multiple phagocytes are capable of hyperactivation in response to oxPAPC, with CD14 acting as the earliest regulator in this process, serving to capture and transport these lipids to promote inflammatory cell fate decisions.

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Crossref · 10.1016/j.immuni.2017.09.010

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  • OxPLs in oxLDL activate endothelial cells and control endothelial barrier permeability, and oxPLs released from dying cells are captured by CD14 on dendritic cells, causing inflammasome-dependent phagocyte hyperactivation.

    “the oxPLs present in oxLDL activate endothelial cells and control the endothelial barrier permeability52,53, and oxPLs released from dying cells are captured by the CD14 receptor on dendritic cells, with ensuing inflammasome-dependent phagocyte hyperactivation54.”

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Authors
Zanoni, I., Tan, Y., Di Gioia, M., Springstead, J. R., & Kagan, J. C.
Affiliations
  • Boston Children's Hospital (US)
  • Western Michigan University (US)
Corresponding author
  • Zanoni, Ivan
  • Kagan, Jonathan C.
Venue
Immunity
Publisher
Elsevier BV
Published
2017-10
Volume
47
Issue
4
Pages
697-709.e3
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2765337093
Cited by
221
References
37
Citations by year
2026: 17 · 2025: 34 · 2024: 27 · 2023: 29 · 2022: 20 · 2021: 35 · 2020: 24 · 2019: 16 · 2018: 16 · 2017: 3
FWCI
7.30
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion, other-oa)
Funders
  • NIH (AI093589, AI116550, P30 DK34854, 1R01AI121066-01A1, 1R01DK115217, P30 DK034854, 1R15HL121770-01A1)
  • Burroughs Wellcome Fund
  • Harvard Medical School Milton Found
  • CCFA Senior Research Awards (412708)
  • Cariplo Foundation (2014-0859)
  • Jane Coffin Childs Fund
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
CD14, OxPAPC, inflammasome, macrophage activation, lipopolysaccharide receptor, sepsis, phagocyte activation
MeSH terms
Animals, Cell Line, Cell Survival, Dendritic Cells, Endocytosis, Female, Flow Cytometry, Humans, Interleukin-1, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Phagocytes, Phosphatidylcholines, Blotting, Western, Mice, Knockout, Lipopolysaccharide Receptors, Adaptive Immunity, HEK293 Cells, Inflammasomes

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