Signaling Lymphocytic Activation Molecule Family-7 Alleviates Corneal Inflammation by Promoting M2 Polarization
Signaling Lymphocytic Activation Molecule Family-7 Alleviates Corneal Inflammation by Promoting M2 Polarization
复制标题
信号淋巴细胞激活分子家族 7 通过促进 M2 极化减轻角膜炎症
DOI：
10.1093/infdis/jiaa445
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发表时间：
2021-03-01
影响因子：
6.4
通讯作者：
Wu, Minhao
中科院分区：
文献类型：
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作者：
Zhu, Siying;Chen, Yu;Wu, Minhao
背景信号传导淋巴细胞活化分子家族7（SLAMF 7）在抗肿瘤免疫中作为巨噬细胞上的免疫检查点分子起作用。然而，其在细菌感染中的作用在很大程度上仍然未知。将从野生型（WT）或SLAMF 7敲除（KO）小鼠分离的骨髓源性巨噬细胞（BMDM）用细菌感染或用脂多糖/干扰素-γ处理以研究SLAMF 7在巨噬细胞极化中的表达和功能。建立铜绿假单胞菌角膜炎小鼠模型以分别使用WT与SLAMF 7 KO小鼠或重组SLAMF 7与磷酸盐缓冲盐水处理的小鼠来探索SLAMF 7对铜绿假单胞菌角膜炎的作用。SLAMF 7的表达增强M1极化或细菌感染的巨噬细胞，并在铜绿假单胞菌感染的小鼠角膜浸润巨噬细胞。SLAMF 7通过诱导STAT 6活化促进M2极化。体内数据显示，SLAMF 7 KO加重了角膜炎症和疾病严重程度，而用重组SLAMF 7治疗减轻了角膜炎症和疾病严重程度。此外，通过Arg-1抑制剂阻断M2极化可消除重组SLAMF 7在疾病进展中的作用。在M1极化或细菌感染时诱导巨噬细胞中的SLAMF 7表达，并通过促进M2极化减轻角膜炎症和铜绿假单胞菌角膜炎的疾病进展。这些发现可能为铜绿假单胞菌角膜炎的治疗提供一种潜在的策略。
Background. Signaling lymphocytic activation molecule family-7 (SLAMF7) functions as an immune checkpoint molecule on macrophages in antitumor immunity. However, its role in bacterial infection remains largely unknown.Methods. Bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) or SLAMF7 knockout (KO) mice were infected with bacteria or treated with lipopolysaccharide/interferon-gamma to investigate the expression and function of SLAMF7 in macrophage polarization. A Pseudomonas aeruginosa keratitis murine model was established to explore the effect of SLAMF7 on P. aeruginosa keratitis using WT vs SLAMF7 KO mice, or recombinant SLAMF7 vs phosphate-buffered saline-treated mice, respectively.Results. SLAMF7 expression was enhanced on M1-polarized or bacterial-infected macrophages, and infiltrating macrophages in P aeruginosa-infected mouse corneas. SLAMF7 promoted M2 polarization by inducing STAT6 activation. In vivo data showed that SLAMF7 KO aggravated, while treatment with recombinant SLAMF7 alleviated, corneal inflammation and disease severity. In addition, blockage of M2 polarization by Arg-1 inhibitor abrogated the effect of recombinant SLAMF7 in disease progression.Conclusions. SLAMF7 expression in macrophages was induced upon M1 polarization or bacterial infection and alleviated corneal inflammation and disease progression of P. aeruginosa keratitis by promoting M2 polarization. These findings may provide a potential strategy for the treatment of P. aeruginosa keratitis.