Pseudomonas aeruginosa (PA) is one of the most common Gram-negative bacteria causing hospital-acquired pulmonary infection, with high drug resistance and mortality. Therefore, it is urgent to introduce new non-antibiotic treatment strategies. Mesenchymal stem cells (MSCs), as important members of the stem cell family, were demonstrated to alleviate pathological damage in acute lung injury. However, the potential mechanism how MSC alleviate acute lung infection caused by PA remains unclear.

The purpose of this study was to investigate the effects of Adipose-derived mesenchymal stem cells (ASCs) on acute pulmonary infections and the possible mechanisms how ASCs reduce pulmonary inflammation induced by PA.

The therapeutic and mechanistic effects of ASCs on PA pulmonary infection were evaluated respectively in a murine model as well as in an in vitro model stimulated by PA and co-cultured with ASCs.

1. ASCs treatment significantly reduced the bacterial load, inflammation of lung tissue and histopathological damage by PA. 2. PA infection mainly activated Nod-like receptor containing a caspase activating and recruitment domain 4 (NLRC4) inflammasome in the lung of mice. ASCs attenuated acute lung infection in mice by inhibiting NLRC4 inflammasome activation. 3. NLRC4^−/− mice showed a significant improvement in survival rate and lung bacterial load after PA infection. 4. ASCs mainly increased expression and secretion of STC‐1 in response to PA‐stimulated NLRC4 inflammasome activation.

PA infection attenuated macrophage phagocytosis through activation of NLRC4 inflammasome in macrophages, which eventually led to pulmonary inflammatory damage in mouse; ASCs reduced the activation of NLRC4 inflammasome in macrophages induced by PA infection, thereby increasing the phagocytic ability of macrophages, and ultimately improving lung tissue damage in mouse; ASCs may inhibit NLRC4 inflammasome through the secretion of STC-1.

铜绿假单胞菌（PA）是引起医院获得性肺部感染的最常见革兰氏阴性细菌之一，具有较高的耐药性和死亡率。因此，迫切需要引入新的非抗生素治疗策略。间充质干细胞（MSCs），作为干细胞家族的重要成员，被证明可以减轻急性肺损伤中的病理损伤。但是，MSC如何减轻PA引起的急性肺部感染的潜在机制仍不清楚。

这项研究的目的是调查脂肪来源的间充质干细胞（ASCs）对急性肺部感染的影响以及ASCs减轻PA引起的肺部炎症的可能机制。

在小鼠模型和小鼠模型中分别评估了ASCs对PA肺部感染的治疗和机制作用。 体外 PA刺激并与ASC共培养的动物模型。

1. ASCs治疗可显着减轻PA引起的细菌负荷，肺组织炎症和组织病理学损害。2. PA感染主要是激活了小鼠肺中含有caspase激活和募集结构域4（NLRC4）炎性小体的Nod样受体。ASC通过抑制NLRC4炎性小体激活来减轻小鼠的急性肺部感染。3. NLRC4 ^-/-小鼠在PA感染后显示出存活率和肺细菌负荷的显着改善。4. ASCs主要是响应PA刺激的NLRC4炎性小体激活而增加STC-1的表达和分泌。

PA感染通过激活巨噬细胞中的NLRC4炎性小体而减弱了巨噬细胞的吞噬作用，最终导致小鼠肺部炎症性损伤。ASCs减少了PA感染诱导的巨噬细胞中NLRC4炎性小体的活化，从而增强了巨噬细胞的吞噬能力，​​并最终改善了小鼠的肺组织损伤。ASC可通过STC-1的分泌抑制NLRC4炎性体。