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Cited by 141Neutrophil, Myeloperoxidase and Oxidative MechanismsImmune Response and Inflammationinterferon and immune responses

Human neutrophils produce interferon gamma upon stimulation by interleukin-12

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Ethuin, Frédéric, Gérard, Bénédicte, Benna, Jamel E, Boutten, Anne, Gougereot-Pocidalo, Marie-Anne, Jacob, Laurent, Chollet-Martin, Sylvie·2004·Laboratory Investigation
DOI 10.1038/labinvest.3700148
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Abstract

Interferon gamma (IFNgamma) is a Th1 cytokine mainly produced by T cells, NK cells and macrophages in response to interleukin (IL)-12. As polymorphonuclear neutrophils (PMN) have been shown to produce and to release numerous cytokines, in particular upon IL-12 stimulation, we investigated the ability of highly purified PMN to secrete IFNgamma. We found that PMN contained a small store of IFNgamma, and that this store was rapidly secreted upon stimulation by degranulating agents such as formyl peptides. Moreover, after a few hours of stimulation with appropriate agents, PMN synthesized IFNgamma. The effect of IL-12 was time- and concentration-dependent, and IL-12 combinations with IL-2, IL-15, IL-18 or LPS were highly synergistic. Cycloheximide inhibited IFNgamma release in such optimal conditions, confirming the ability of PMN to synthesize IFNgamma. IFNgamma synthesis was associated with an increase in specific mRNA content, pointing to a transcriptional mechanism. The IFNgamma produced by PMN was biologically active, as demonstrated by its ability to induce TNFalpha synthesis by PMN themselves or to induce IL-10 synthesis by peripheral blood mononuclear cells. These findings reveal a novel pathway of autocrine and paracrine PMN activation. They also identified a new role for IFNgamma, bridging innate and adaptive immune responses.

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  • Interferon-γ released by activated neutrophils induces macrophage activation.

    “Interferon-γ released by activated neutrophils induces macrophage activation [219].”

    From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [219]

  • Neutrophils release MPO, which is taken up by residential macrophages expressing macrophage mannose receptors (MMR).

    “Neutrophils release MPO, which is taken up by residential macrophages expressing macrophage mannose receptors (MMR).”

    From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [219]

  • The interaction between MPO and MMRs leads to the release of ROS and proinflammatory cytokines (IL-6, IL-8, TNF-α, IL-1, GM-CSF) by macrophages.

    “The interaction between MPO and MMRs leads to the release of ROS (reactive oxygen species) and proinflammatory cytokines (IL-6, IL-8, TNF-α, IL-1, GM-CSF) by macrophages.”

    From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [219]

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  1. Ho ¨flich C, Sabat R, Rosseau S, et al. Naturally occuring anti-IFN-g auto-antibody and severe infections with Mycobacterium cheloneae and Burkholderia cocovene- mans. Blood 2004;103:673-675.

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Authors
Ethuin, F., Gérard, B., Benna, J. E., Boutten, A., Gougereot-Pocidalo, M.-A., Jacob, L., & Chollet-Martin, S.
Affiliations
  • Inserm (FR)
  • Hôpital Bichat-Claude-Bernard (FR)
  • Hôpital Saint-Louis (FR)
ORCID
Venue
Laboratory Investigation
Publisher
Elsevier BV
Published
2004-10
Volume
84
Issue
10
Pages
1363-1371
ISSN
0023-6837 (ISSN-L)
DOI
10.1038/labinvest.3700148
OpenAlex
W2014770545
Cited by
141
References
49
Citations by year
2026: 4 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 6 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 6 · 2013: 11 · 2012: 11
FWCI
1.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Laboratory Investigation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
interferon-gamma, neutrophils, IL-12, cytokine production, degranulation, formyl peptides, cytokine synergy, IL-15, IL-18, lipopolysaccharide, autocrine activation, innate-adaptive immune bridge, TNF-alpha induction, transcriptional regulation
MeSH terms
Adjuvants, Immunologic, Cell Separation, Cells, Cultured, Dose-Response Relationship, Drug, Humans, Interferon-gamma, Lipopolysaccharides, Lymphocyte Activation, N-Formylmethionine Leucyl-Phenylalanine, Neutrophils, RNA, Messenger, Blotting, Western, Cell Degranulation, Interleukin-12, Interleukin-15, Reverse Transcriptase Polymerase Chain Reaction

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