本期文章：《免疫》：Online/在线发表

美国国立卫生研究院Keisuke Nagao研究组发现，巨噬细胞介导的细胞外基质重塑控制宿主皮肤的金黄色葡萄球菌敏感性。这一研究成果发表在2023年7月3日出版的国际学术期刊《免疫》上。

鉴于巨噬细胞在组织重塑中的重要性，他们研究了皮下巨噬细胞(HDMs)及其对宿主感染易感性的影响。大量和单细胞转录组学揭示了HDM亚群与CCR2二分法。HDM的稳态需要成纤维细胞衍生的生长因子CSF1，该因子的消融使HDM从皮下外膜中消失。CCR2−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感知。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的IGF1。

值得注意的是，HDMs或IGF1的缺失限制了金黄色葡萄球菌通过HA的扩张，并赋予了对蜂窝织炎的保护作用。他们的研究结果揭示了巨噬细胞在HA调节中的作用，对感染结果有影响，这可能被用来限制感染在皮下生态位的建立。

据悉，皮下是引起蜂窝组织炎的金黄色葡萄球菌感染的主要部位。

附：英文原文

Title: Macrophage-mediated extracellular matrix remodeling controls host Staphylococcus aureus susceptibility in the skin

Author: Benjamin Voisin, Vinod Nadella, Thomas Doebel, Shubham Goel, Keiko Sakamoto, Otgonzaya Ayush, Jay-Hyun Jo, Michael C. Kelly, Tetsuro Kobayashi, Jean X. Jiang, Ying Hu, Chunhua Yan, Keisuke Nagao

Issue&Volume: 2023-07-03

Abstract: Hypodermis is the predominant site of Staphylococcus aureus infections that cause cellulitis. Given the importance of macrophages in tissue remodeling,we examined the hypodermal macrophages (HDMs) and their impact on host susceptibilityto infection. Bulk and single-cell transcriptomics uncovered HDM subsets with CCR2-dichotomy.HDM homeostasis required the fibroblast-derived growth factor CSF1, ablation of whichabrogated 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-autonomousIGF1 was required for accessibility of AP-1 transcription factor motifs that controlledLYVE-1 expression. Remarkably, loss of HDMs or IGF1 limited Staphylococcus aureus expansion via HA and conferred protection against cellulitis. Our findings reveala 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.

DOI: 10.1016/j.immuni.2023.06.006