Institut Pasteur, Biology of Infection Unit, 75015 Paris, France; Inserm U1117, 75015 Paris, France.
Institut Pasteur, Human Histopathology and Animal Models Unit, 75015 Paris, France.
Immunity. 2015 Jan 20;42(1):145-58. doi: 10.1016/j.immuni.2014.12.020. Epub 2014 Dec 25.
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.
库普弗细胞（Kupffer cells）是一种来源于胎儿的吞噬细胞，排列在肝窦内，是宿主防御肠侵袭性细菌的主要贡献者。在这里，我们发现李斯特菌（Listeria monocytogenes）感染诱导库普弗细胞的早期坏死性死亡，随后单核细胞募集和抗细菌 1 型炎症反应。库普弗细胞死亡还触发了涉及肝细胞衍生警报素白细胞介素-33（IL-33）和嗜碱性粒细胞衍生白细胞介素-4（IL-4）的 2 型反应。这导致募集到肝脏的单核细胞衍生巨噬细胞的替代激活，从而取代了被消融的库普弗细胞并恢复了肝脏的内稳态。因此，库普弗细胞死亡是感染时协调 1 型杀菌炎症和 2 型介导的肝脏修复的关键信号。这表明，除了经典的 1 型和 2 型反应的二分法之外，这些反应可以在细菌感染的背景下依次发展，并相互依存，分别协调肝脏免疫反应和恢复内稳态。
