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TLR7 在上皮屏障处的激活促进紧急骨髓生成和肺部抗病毒免疫。

TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung antiviral immunity.

机构信息

Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.

National Heart and Lung Institute, Imperial College London, London, United Kingdom.

出版信息

Elife. 2023 Aug 11;12:e85647. doi: 10.7554/eLife.85647.

DOI:10.7554/eLife.85647
PMID:37566453
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10465127/
Abstract

Monocytes are heterogeneous innate effector leukocytes generated in the bone marrow and released into circulation in a CCR2-dependent manner. During infection or inflammation, myelopoiesis is modulated to rapidly meet the demand for more effector cells. Danger signals from peripheral tissues can influence this process. Herein we demonstrate that repetitive TLR7 stimulation via the epithelial barriers drove a potent emergency bone marrow monocyte response in mice. This process was unique to TLR7 activation and occurred independently of the canonical CCR2 and CX3CR1 axes or prototypical cytokines. The monocytes egressing the bone marrow had an immature Ly6C-high profile and differentiated into vascular Ly6C-low monocytes and tissue macrophages in multiple organs. They displayed a blunted cytokine response to further TLR7 stimulation and reduced lung viral load after RSV and influenza virus infection. These data provide insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites.

摘要

单核细胞是骨髓中产生的异质性先天效应白细胞，以 CCR2 依赖的方式释放到循环中。在感染或炎症期间，髓样细胞生成会被调节以迅速满足对更多效应细胞的需求。来自外周组织的危险信号可以影响这个过程。本文中，我们证明了上皮屏障中 TLR7 的重复刺激在小鼠中引发了强烈的应急骨髓单核细胞反应。这个过程是 TLR7 激活所特有的，并且独立于经典的 CCR2 和 CX3CR1 轴或典型的细胞因子。从骨髓中迁出的单核细胞具有不成熟的 Ly6C-高表型，并在多个器官中分化为血管 Ly6C-低单核细胞和组织巨噬细胞。它们对进一步的 TLR7 刺激的细胞因子反应减弱，并且在 RSV 和流感病毒感染后肺部病毒载量降低。这些数据提供了对可能发生于屏障部位遇到单链 RNA 病毒时的应急髓样细胞生成的深入了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a664/10465127/73cb675cda0f/elife-85647-sa2-fig1.jpg
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