Macrophage-mediated extracellular matrix remodeling controls host Staphylococcus aureus susceptibility in the skin.
Macrophage-mediated extracellular matrix remodeling controls host Staphylococcus aureus susceptibility in the skin.
复制标题
巨噬细胞介导的细胞外基质重塑控制皮肤中宿主金黄色葡萄球菌的敏感性。
DOI：
10.1016/j.immuni.2023.06.006
复制
发表时间：
2023
期刊：
影响因子：
32.4
通讯作者：
Nagao,Keisuke
中科院分区：
文献类型：
--
作者：
Voisin,Benjamin;Nadella,Vinod;Doebel,Thomas;Goel,Shubham;Sakamoto,Keiko;Ayush,Otgonzaya;Jo,Jay-Hyun;Kelly,MichaelC;Kobayashi,Tetsuro;Jiang,JeanX;Hu,Ying;Yan,Chunhua;Nagao,Keisuke
皮下组织是引起蜂窝织炎的金黄色葡萄球菌感染的主要部位。鉴于巨噬细胞在组织重塑中的重要性，我们研究了皮下巨噬细胞（HDM）及其对宿主感染易感性的影响。批量和单细胞转录组学发现了具有CCR 2二分法的HDM子集。HDM稳态需要成纤维细胞衍生的生长因子CSF 1，其消融从下皮外膜废除HDM。CCR 2 −HDMs的缺失导致细胞外基质成分透明质酸（HA）的积累。HDM介导的HA清除需要HA受体LYVE-1的感应。控制LYVE-1表达的AP-1转录因子基序的可及性需要细胞自主性IGF 1。值得注意的是，HDMs或IGF 1的缺失限制了金黄色葡萄球菌通过HA的扩增，并赋予了对蜂窝织炎的保护作用。我们的研究结果揭示了巨噬细胞在HA调节中的功能，其对感染结果具有影响，这可能被利用来限制皮下生态位中感染的建立。
Hypodermis is the predominant site ofStaphylococcus aureusinfections that cause cellulitis. Given the importance of macrophages in tissue remodeling, we examined the hypodermal macrophages (HDMs) and their impact on host susceptibility to infection. Bulk and single-cell transcriptomics uncovered HDM subsets with CCR2-dichotomy. HDM homeostasis required the fibroblast-derived growth factor CSF1, ablation of which abrogated HDMs from the hypodermal adventitia. Loss of CCR2−HDMs resulted in accumulation of the extracellular matrix component, hyaluronic acid (HA). HDM-mediated HA clearance required sensing by the HA receptor, LYVE-1. Cell-autonomous IGF1 was required for accessibility of AP-1 transcription factor motifs that controlled LYVE-1 expression. Remarkably, loss of HDMs or IGF1 limitedStaphylococcus aureusexpansion via HA and conferred protection against cellulitis. Our findings reveal a function for macrophages in the regulation of HA with an impact on infection outcomes, which may be harnessed to limit the establishment of infection in the hypodermal niche.