Staphylococcus aureus is the main cause of septic arthritis in humans, a disease associated with high morbidity and mortality. Inflammation triggered in response to infection is fundamental to control bacterial growth but may cause permanent tissue damage. Here, we evaluated the role of Lipoxin A4 (LXA4) in S aureus‐induced arthritis in mice. Septic arthritis was induced by S aureus injection into tibiofemoral joints. At different time points, we evaluated cell recruitment and bacterial load in the joint, the production of pro‐inflammatory molecules, and LXA4 in inflamed tissue and analyzed joint damage and dysfunction. LXA4 was investigated using genetically modified mice or by pharmacological blockade of its synthesis and receptor. CD11c+ cells were evaluated in lymph nodes by confocal microscopy and flow cytometry and dendritic cell chemotaxis using the Boyden chamber. Absence or pharmacological blockade of 5‐lipoxygenase (5‐LO) reduced joint inflammation and dysfunction and was associated with better control of infection at 4 to 7 days after the infection. There was an increase in LXA4 in joints of S aureus‐infected mice and administration of LXA4 reversed the phenotype in 5‐LO−/− mice. Blockade or absence of the LXA4 receptor FPR2 has a phenotype similar to 5‐LO−/− mice. Mechanistically, LXA4 appeared to control migration and function of dendritic cells, cells shown to be crucial for adequate protective responses in the model. Thus, after the first days of infection when symptoms become evident therapies that inhibit LXA4 synthesis or action could be useful for treatment of S aureus‐induced arthritis.

中文翻译：

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脂氧素 A 4 削弱有效的细菌控制并增强金黄色葡萄球菌感染引起的关节炎症和损伤

金黄色葡萄球菌是人类化脓性关节炎的主要原因，该疾病与高发病率和死亡率相关。感染引起的炎症是控制细菌生长的基础，但可能会导致永久性组织损伤。在这里，我们评估了脂氧素 A4（LXA4）在金黄色葡萄球菌诱导的小鼠关节炎中的作用。化脓性关节炎是由金黄色葡萄球菌注射到胫股关节引起的。在不同的时间点，我们评估了关节中的细胞募集和细菌负荷、炎症组织中促炎分子的产生和 LXA4，并分析了关节损伤和功能障碍。LXA4 使用转基因小鼠或通过其合成和受体的药理学封锁进行了研究。通过共聚焦显微镜和流式细胞术以及使用 Boyden 室的树突状细胞趋化性评估淋巴结中的 CD11c+ 细胞。5-脂氧合酶 (5-LO) 的缺失或药物阻断可减少关节炎症和功能障碍，并与感染后 4 至 7 天更好地控制感染有关。金黄色葡萄球菌感染小鼠关节中的 LXA4 增加，并且 LXA4 的给药逆转了 5-LO-/- 小鼠的表型。LXA4 受体 FPR2 的阻断或缺失具有与 5-LO-/- 小鼠相似的表型。从机制上讲，LXA4 似乎控制树突细胞的迁移和功能，这些细胞对模型中的足够保护反应至关重要。因此，