A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment

Sierro, Frédéric; Evrard, Maximilien; Rizzetto, Simone; Melino, Michelle; Mitchell, Andrew J.; Florido, Mário; Beattie, Lynette; Walters, Shaun B.; Tay, Szun S.; Lü, Bo; Holz, Lauren E.; Roediger, Ben; Wong, Yik Chun; Warren, Alessandra; Ritchie, William; McGuffog, Claire; Weninger, Wolfgang; Couteur, David G. Le; Ginhoux, Florent; Britton, Warwick J.; Heath, William R.; Saunders, Bernadette M.; McCaughan, Geoffrey W.; Luciani, Fabio; MacDonald, Kelli P. A.; Ng, Lai Guan; Bowen, David G.; Bertolino, Patrick

doi:10.1016/j.immuni.2017.07.018

Cited by 193 publications

(204 citation statements)

References 54 publications

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“…However, it has to be kept in mind that the hepatic capsule harbors a unique cellular network of macrophages phenotypically distinct from KCs that restricts the hepatic dissemination of intraperitoneal bacteria. (70)…”

Section: Peritoneal Macrophagesmentioning

confidence: 99%

Liver Macrophages: Old Dogmas and New Insights

2019

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Inflammation is a hallmark of virtually all liver diseases, such as liver cancer, fibrosis, nonalcoholic steatohepatitis, alcoholic liver disease, and cholangiopathies. Liver macrophages have been thoroughly studied in human disease and mouse models, unravelling that the hepatic mononuclear phagocyte system is more versatile and complex than previously believed. Liver macrophages mainly consist of liver-resident phagocytes, or Kupffer cells (KCs), and bone marrow-derived recruited monocytes. Although both cell populations in the liver demonstrate principal functions of macrophages, such as phagocytosis, danger signal recognition, cytokine release, antigen processing, and the ability to orchestrate immune responses, KCs and recruited monocytes retain characteristic ontogeny markers and remain remarkably distinct on several functional aspects. While KCs dominate the hepatic macrophage pool in homeostasis ("sentinel function"), monocyte-derived macrophages prevail in acute or chronic injury ("emergency response team"), making them an interesting target for novel therapeutic approaches in liver disease. In addition, recent data acquired by unbiased large-scale techniques, such as single-cell RNA sequencing, unraveled a previously unrecognized complexity of human and murine macrophage polarization abilities, far beyond the old dogma of inflammatory (M1) and anti-inflammatory (M2) macrophages. Despite tremendous progress, numerous challenges remain in deciphering the full spectrum of macrophage activation and its implication in either promoting liver disease progression or repairing injured liver tissue. Being aware of such heterogeneity in cell origin and function is of crucial importance when studying liver diseases, developing novel therapeutic interventions, defining macrophage-based prognostic biomarkers, or designing clinical trials. Growing knowledge in gene expression modulation and emerging technologies in drug delivery may soon allow shaping macrophage populations toward orchestrating beneficial rather than detrimental inflammatory responses. (Hepatology Communications 2019;3:730-743). T he liver is the largest solid organ and exerts vital metabolic functions. Liver diseases leading to liver cirrhosis or cancer are increasingly challenging for public health, the current trend being an augmentation of such diseases mainly caused by changes in alimentation and life habits. (1) Liver diseases are various by nature in terms of etiologies, chronicity, and chances of recovery. However, one constant feature is the presence of liver inflammation, and most remarkably, there is an apparent compulsory association of inflammation with a poor outcome for patients. (2-6) Liver macrophages are included in the mononuclear phagocyte system and are renown cornerstones in most if not all inflammation-related liver disorders due to their ability to respond to a seemingly infinite

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Section: Peritoneal Macrophagesmentioning

confidence: 99%

Liver Macrophages: Old Dogmas and New Insights

2019

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“…(19) These data suggest that tissue repair Ly-6C Low/monocytes contribute to the resolution of CF. A recent study identified F4/80 + capsular macrophages beneath the liver surface, (29) but the F4/80monocytes we analyzed appear to be different cell types.…”

Section: Discussionmentioning

confidence: 64%

Development of Capsular Fibrosis Beneath the Liver Surface in Humans and Mice

Balog

Ogawa

et al. 2019

Hepatology

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Glisson's capsule is the connective tissue present in the portal triad as well as beneath the liver surface. Little is known about how Glisson's capsule changes its structure in capsular fibrosis (CF), which is characterized by fibrogenesis beneath the liver surface. In this study, we found that the human liver surface exhibits multilayered capsular fibroblasts and that the bile duct is present beneath the mesothelium, whereas capsular fibroblasts are scarce and no bile ducts are present beneath the mouse liver surface. Patients with cirrhosis caused by alcohol abuse or hepatitis C virus infection show development of massive CF. To examine the effect of alcohol on CF in mice, we first injected chlorhexidine gluconate (CG) intraperitoneally and then fed alcohol for 1 month. The CG injection induces CF consisting of myofibroblasts beneath the mesothelium. One month after CG injection, the fibrotic area returns to the normal structure. In contrast, additional alcohol feeding sustains the presence of myofibroblasts in CF. Cell lineage tracing revealed that mesothelial cells give rise to myofibroblasts in CF, but these myofibroblasts disappear 1 month after recovery with or without alcohol feeding. Capsular fibroblasts isolated from the mouse liver spontaneously differentiated into myofibroblasts and their differentiation was induced by transforming growth factor beta 1 (TGF‐β1) or acetaldehyde in culture. In alcohol‐fed mice, infiltrating CD11b+Ly‐6CLow/– monocytes had reduced mRNA expression of matrix metalloproteinase 13 and matrix metalloproteinase 9 and increased expression of tissue inhibitor of matrix metalloproteinase 1, Tgfb1, and interleukin‐10 during resolution of CF. Conclusion: The present study revealed that the structure of Glisson's capsule is different between human and mouse livers and that alcohol impairs the resolution of CF by changing the phenotype of Ly‐6CLow/– monocytes.

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“…Twenty‐two years later, Tadeusz Browicz correctly identified them as a large population of liver‐resident macrophages. KCs are widely distributed within the liver, but they are not evenly spread . KCs are usually present in areas away from larger vessels, and they exclusively inhabit the sinusoidal intravascular compartment and are anchored to the liver sinusoidal endothelial cells (LSECs).…”

Section: Myeloid Lineagementioning

confidence: 99%

“…However, CX3CR1 marker is expressed on DCs, but not on mature KCs under homeostatic conditions, making this chemokine receptor useful for identification of DCs both in vivo and in vitro. However, a recent publication has challenged this concept suggesting that CX3CR1+ cells that reside underneath the liver capsule are a population of macrophages . Functional assays and specific CX3CR1‐mediated cell depletion will be crucial to further determine the exact function of these cells.…”

Section: Myeloid Lineagementioning

confidence: 99%

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The liver as a nursery for leukocytes

Mafra

Nakagaki

Oliveira

et al. 2019

Journal of Leukocyte Biology

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Leukocytes are a large population of cells spread within most tissues in the body. These cells may be either sessile (called as resident cells) or circulating leukocytes, which travel long journeys inside the vessels during their lifespan. Although production and maturation of these leukocytes in adults primarily occur in the bone marrow, it is well known that this process—called hematopoiesis—started in the embryonic life in different sites, including the yolk sac, placenta, and the liver. In this review, we will discuss how the liver acts as a pivotal site for leukocyte maturation during the embryo phase, and also how the most frequent liver‐resident immune cell populations—namely Kupffer cells, dendritic cells, and lymphocytes—play a vital role in both tolerance and inflammatory responses to antigens from food, microbiota, and pathogens.

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A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment

Cited by 193 publications

References 54 publications

Liver Macrophages: Old Dogmas and New Insights

Liver Macrophages: Old Dogmas and New Insights

Development of Capsular Fibrosis Beneath the Liver Surface in Humans and Mice

The liver as a nursery for leukocytes

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