The lung epithelium constitutes the first barrier against invading pathogens and also a major surface potentially exposed to nanoparticles. In order to ensure and preserve lung epithelial barrier function, the alveolar compartment possesses local defence mechanisms that are able to control bacterial infection. For instance, alveolar macrophages are professional phagocytic cells that engulf bacteria and environmental contaminants (including nanoparticles) and secrete pro-inflammatory cytokines to effectively eliminate the invading bacteria/contaminants. The consequences of nanoparticle exposure in the context of lung infection have not been studied in detail. Previous reports have shown that sequential lung exposure to nanoparticles and bacteria may impair bacterial clearance resulting in increased lung bacterial loads, associated with a reduction in the phagocytic capacity of alveolar macrophages. Here we have studied the consequences of SiO2 nanoparticle exposure on Pseudomonas aeruginosa clearance, Pseudomonas aeruginosa-induced inflammation and lung injury in a mouse model of acute pneumonia. We observed that pre-exposure to SiO2 nanoparticles increased mice susceptibility to lethal pneumonia but did not modify lung clearance of a bioluminescent Pseudomonas aeruginosa strain. Furthermore, internalisation of SiO2 nanoparticles by primary alveolar macrophages did not reduce the capacity of the cells to clear Pseudomonas aeruginosa. In our murine model, SiO2 nanoparticle pre-exposure preferentially enhanced Pseudomonas aeruginosa-induced lung permeability (the latter assessed by the measurement of alveolar albumin and IgM concentrations) rather than contributing to Pseudomonas aeruginosa-induced lung inflammation (as measured by leukocyte recruitment and cytokine concentration in the alveolar compartment). We show that pre-exposure to SiO2 nanoparticles increases mice susceptibility to lethal pneumonia but independently of macrophage phagocytic function. The deleterious effects of SiO2 nanoparticle exposure during Pseudomonas aeruginosa-induced pneumonia are related to alterations of the alveolar-capillary barrier rather than to modulation of the inflammatory responses.

中文翻译：

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在铜绿假单胞菌肺炎的小鼠模型中，急性暴露于二氧化硅纳米颗粒会增加死亡率并增加肺通透性。

肺上皮是抵御病原体入侵的第一道屏障，也是潜在暴露于纳米颗粒的主要表面。为了确保和保持肺上皮屏障功能，肺泡隔室具有能够控制细菌感染的局部防御机制。例如，肺泡巨噬细胞是吞噬细菌和环境污染物（包括纳米颗粒）的专业吞噬细胞，并分泌促炎细胞因子以有效消除入侵的细菌/污染物。尚未详细研究在肺部感染中纳米颗粒暴露的后果。先前的报道表明，肺部连续接触纳米颗粒和细菌可能会损害细菌清除率，从而导致肺部细菌负荷增加，与肺泡巨噬细胞吞噬能力降低有关。在这里，我们研究了在急性肺炎小鼠模型中SiO2纳米颗粒暴露对铜绿假单胞菌清除，铜绿假单胞菌诱导的炎症和肺损伤的后果。我们观察到，预先暴露于SiO2纳米颗粒会增加小鼠对致命性肺炎的敏感性，但不会改变生物发光的铜绿假单胞菌菌株的肺部清除率。此外，初级肺泡巨噬细胞对SiO2纳米颗粒的内在化没有降低细胞清除铜绿假单胞菌的能力。在我们的鼠模型中 SiO2纳米颗粒预暴露优先增强了铜绿假单胞菌诱导的肺通透性（后者通过测量肺泡白蛋白和IgM浓度进行评估），而不是助长了铜绿假单胞菌诱导的肺部炎症（如通过白细胞募集和肺泡腔室中的细胞因子浓度测量） ）。我们表明，预先暴露于SiO2纳米颗粒会增加小鼠对致死性肺炎的易感性，但与巨噬细胞的吞噬功能无关。铜绿假单胞菌诱发的肺炎期间SiO2纳米颗粒暴露的有害作用与肺泡-毛细血管屏障的改变有关，而不是与炎症反应的调节有关。