Program of Infection and Immunology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
J Infect Dis. 2021 Mar 3;223(5):854-865. doi: 10.1093/infdis/jiaa445.
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.
Bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) or SLAMF7 knockout (KO) mice were infected with bacteria or treated with lipopolysaccharide/interferon-γ 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.
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.
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.
信号淋巴细胞激活分子家族 7（SLAMF7）在抗肿瘤免疫中作为巨噬细胞上的免疫检查点分子发挥作用。然而，其在细菌感染中的作用在很大程度上尚不清楚。
从野生型（WT）或 SLAMF7 敲除（KO）小鼠的骨髓来源的巨噬细胞（BMDM）中分离出巨噬细胞，用细菌感染或用脂多糖/干扰素-γ处理，以研究 SLAMF7 在巨噬细胞极化中的表达和功能。建立绿脓假单胞菌角膜炎小鼠模型，分别使用 WT 与 SLAMF7 KO 小鼠、重组 SLAMF7 与磷酸盐缓冲盐水处理的小鼠，来研究 SLAMF7 对绿脓假单胞菌角膜炎的影响。
SLAMF7 在 M1 极化或细菌感染的巨噬细胞以及绿脓假单胞菌感染的小鼠角膜中的浸润巨噬细胞上表达增强。SLAMF7 通过诱导 STAT6 激活促进 M2 极化。体内数据显示，SLAMF7 KO 加重了角膜炎症和疾病的严重程度，而用重组 SLAMF7 处理则缓解了这一情况。此外，通过 Arg-1 抑制剂阻断 M2 极化，可消除重组 SLAMF7 在疾病进展中的作用。
SLAMF7 在巨噬细胞中的表达在 M1 极化或细菌感染时被诱导，并通过促进 M2 极化来减轻绿脓假单胞菌角膜炎的角膜炎症和疾病进展。这些发现可能为绿脓假单胞菌角膜炎的治疗提供一种潜在的策略。
