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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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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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“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]
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“In addition to competing for survival signals like CSF-1 (9, 33, 34), infiltrating monocytes actively replace embryonic KCs (EmKCs) during injury (35–37).”
From Macrophage duality in liver diseases: heterogeneity, plasticity, and the quest for precision therapeutics (2026) · cites this paper as [35]
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Metadata
- 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
- bronze
- doi.org
- Licence
- 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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