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

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

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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Crossref · 10.1016/j.immuni.2014.12.020

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  • Basophils can activate fibroblasts in vitro and are an important source of IL-4 in inflammation, signaling to activate M2 macrophages.

    “Basophils can activate fibroblasts in vitro and are an important source of IL-4 in inflammation, signaling to activate M2 macrophages [49].”

    From Osteoimmunology of Fracture Healing. (2024) · cites this paper as [49]

  • Infiltrating monocytes actively replace embryonic Kupffer cells during injury.

    “In addition to competing for survival signals like CSF-1 (9, 33, 34), infiltrating monocytes actively replace embryonic KCs (EmKCs) during injury (35–37).”

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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
Venue
Immunity
Publisher
Elsevier BV
Published
2015-01
Volume
42
Issue
1
Pages
145-158
ISSN
1074-7613 (ISSN-L)
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
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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