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Long Term Intravital Multiphoton Microscopy Imaging of Immune Cells in Healthy and Diseased Liver Using CXCR6.Gfp Reporter Mice
Published on: March 24, 2015
Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair
Camille Blériot1, Théo Dupuis1, Grégory Jouvion2
1Institut Pasteur, Biology of Infection Unit, 75015 Paris, France; Inserm U1117, 75015 Paris, France.
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.
Insights
Kupffer cell death during Listeria infection triggers sequential immune responses. This coordinated inflammation and repair process restores liver homeostasis.
Area of Science:
- Immunology
- Hepatology
- Microbiology
Background:
- Kupffer cells are crucial for liver defense against bacterial pathogens.
- Host defense mechanisms are essential for maintaining liver homeostasis.
Purpose of the Study:
- To investigate the role of Kupffer cells in Listeria monocytogenes infection.
- To elucidate the sequential immune responses following Kupffer cell death.
Main Methods:
- Infection of mice with Listeria monocytogenes.
- Analysis of Kupffer cell death pathways.
- Assessment of monocyte recruitment and macrophage activation.
- Evaluation of type 1 and type 2 immune responses, including cytokine signaling (IL-33, IL-4).
Main Results:
- Listeria monocytogenes infection induced necroptotic death of Kupffer cells.
- Kupffer cell death triggered sequential type 1 (anti-bacterial) and type 2 (IL-33, IL-4 mediated) inflammatory responses.
- Recruited monocytes differentiated into alternatively activated macrophages, replacing dead Kupffer cells and restoring liver homeostasis.
Conclusions:
- Kupffer cell death is a critical signaling event orchestrating both microbicidal inflammation and liver repair.
- Immune responses in the liver can involve sequential, interdependent type 1 and type 2 pathways.
- This study reveals a novel mechanism for liver immune response coordination and restoration of homeostasis post-infection.
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