A distinct population of immune cells found under the fibrous capsule that surrounds the liver has been identified by an international team. The cells, called liver capsular macrophages, protect the liver from bacteria in the peritoneal cavity that lies between the abdominal wall and the membrane covering abdominal organs.
Researchers had observed immune cells in the liver’s capsule almost 30 years ago, but had not agreed on what type they were. Scientists from A*STAR’s Singapore Immunology Network, in collaboration with colleagues in Australia, used a fluorescent imaging technique, called two-photon microscopy to investigate this futher.
They found that their shape was different from Kupffer cells, an immune cell residing in the liver’s tissue that protects it from bacteria circulating in the blood. The combination of molecules on their surface distinguished them from other types of immune cells, including Kupffer cells. When the team analyzed the cells’ gene expression, they found it similar to — and so classified them as — macrophages, a type of white blood cell that engulfs and destroys cellular debris, microbes, and cancer cells.
These newly identified cells have branches, or dendrites, that extend toward bacteria and other foreign substances. They are also involved in recruiting another type of immune cell, neutrophils, to the liver. Neutrophils crawl along the liver capsular macrophages’ dendrites to reach the liver capsule and provide additional immune protection against infection.
When the team analyzed the cells’ gene expression, they found it similar to that of macrophages, a type of white blood cell that engulfs and destroys cellular debris, microbes, and cancer cells, and thus classified it as such. The team also found that these ‘liver capsular macrophages’ were replenished by blood monocytes, unlike Kupffer cells that self-renew.
“This study represents how two-photon microscopy can contribute to the discovery of new immune cell subsets,” says A*STAR immunologist Lai Guan Ng, one of the study’s co-authors. “Our study discovered that liver capsular macrophages serve as sensors for peritoneal bacteria and recruit neutrophils to fight infection. This study shows that the liver has two separate and non-overlapping niches occupied by distinct resident macrophage populations: Kupffer cells in the liver for mediating protection against systemic bacterial infection, and liver capsular macrophages for protection against intraperitoneal infection.”
Ng says he is interested in further investigating how liver capsular macrophages respond to liver diseases, and how they are related to people’s susceptibility to infections.
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network.
- Sierro, F., Evrard, M., Rizzetto, S., Melino, M., Mitchell, A. J. et al. A liver capsular network of monocyte-derived macrophages restricts hepatic dissemination of intraperitoneal bacteria by neutrophil recruitment. Immunity 47, 374–388 (2017).| Article
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