Cited by 471Immune Response and InflammationImmune cells in cancerIL-33, ST2, and ILC Pathways

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Liver-Resident Macrophage Necroptosis Orchestrates Type 1 Microbicidal Inflammation and Type-2-Mediated Tissue Repair during Bacterial Infection

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Blériot, Camille, Dupuis, Théo, Jouvion, Grégory, Eberl, Gérard, Disson, Olivier, Lecuit, Marc·2015·Immunity

DOI 10.1016/j.immuni.2014.12.020

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Abstract

Kupffer cells, the phagocytes of fetal origin that line the liver sinusoids, are key contributors of host defense against enteroinvasive bacteria. Here, we found that infection by Listeria monocytogenes induced the early necroptotic death of Kupffer cells, which was followed by monocyte recruitment and an anti-bacterial type 1 inflammatory response. Kupffer cell death also triggered a type 2 response that involved the hepatocyte-derived alarmin interleukin-33 (IL-33) and basophil-derived interleukin-4 (IL-4). This led to the alternative activation of the monocyte-derived macrophages recruited to the liver, which thereby replaced ablated Kupffer cells and restored liver homeostasis. Kupffer cell death is therefore a key signal orchestrating type 1 microbicidal inflammation and type-2-mediated liver repair upon infection. This indicates that beyond the classical dichotomy of type 1 and type 2 responses, these responses can develop sequentially in the context of a bacterial infection and act interdependently, orchestrating liver immune responses and return to homeostasis, respectively.

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Authors: Blériot, C., Dupuis, T., Jouvion, G., Eberl, G., Disson, O., & Lecuit, M.
Affiliations: Inserm (FR)
Institut Pasteur (FR)
Hôpital Necker-Enfants Malades (FR)
Corresponding author: Lecuit, Marc
ORCID: Blériot, Camille
Dupuis, Théo
Jouvion, Grégory
Eberl, Gérard
Disson, Olivier
Lecuit, Marc
Venue: Immunity
Publisher: Elsevier BV
Published: 2015-01
Volume: 42
Issue: 1
Pages: 145-158
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2014.12.020
OpenAlex: W2082812721
Cited by: 471
References: 68
Citations by year: 2026: 24 · 2025: 35 · 2024: 45 · 2023: 41 · 2022: 42 · 2021: 57 · 2020: 42 · 2019: 35 · 2018: 47 · 2017: 42 · 2016: 41 · 2015: 20
FWCI: 15.67
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: Agence Nationale de la Recherche (ANR-10-LABX-0062)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords: Kupffer cells, necroptosis, Listeria monocytogenes, liver infection, type 1 inflammation, Th2 immune response, IL-33, IL-4, monocyte recruitment, alternative activation, tissue repair, liver homeostasis, hepatic macrophages
MeSH terms: Interleukin-33, Animals, Cell Differentiation, Cells, Cultured, Complement Pathway, Alternative, Homeostasis, Inflammation, Interleukins, Kupffer Cells, Listeriosis, Listeria monocytogenes, Liver, Mice, Inbred Strains, Monocytes, Necrosis, Phagocytosis, Wound Healing, Interleukin-4, Mice

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Liver-Resident Macrophage Necroptosis Orchestrates Type 1 Microbicidal Inflammation and Type-2-Mediated Tissue Repair during Bacterial Infection

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