Pulmonary Expression of Interleukin-17 Contributes to Neutrophil Infiltration into the Lungs during Pneumonic Plague.
Pulmonary Expression of Interleukin-17 Contributes to Neutrophil Infiltration into the Lungs during Pneumonic Plague.
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DOI：
10.1128/iai.00131-23
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发表时间：
2023-07-18
影响因子：
3.1
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中科院分区：
文献类型：
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吸入被鼠疫耶尔森氏菌感染的呼吸道飞沫会导致一种迅速发展和致命的坏死性肺炎，称为原发性肺鼠疫。疾病表现为双相的，具有初始的炎症前阶段，在肺部快速细菌复制，缺乏容易检测到的宿主免疫应答。随后是促炎阶段的开始，其观察到促炎细胞因子的显著上调和肺中广泛的中性粒细胞积聚。纤溶酶原激活物蛋白酶（plasminogen activator protease，Pla）是Y.肺里的鼠疫我们的实验室最近表明，Pla作为一种粘附素，促进与肺泡巨噬细胞的结合，以促进称为Yops的效应蛋白通过3型分泌系统（T3 SS）易位到靶宿主细胞的胞质溶胶中。PLA介导的粘附的丧失破坏了疾病的炎症前阶段，并导致早期中性粒细胞迁移到肺部。虽然已经确定耶尔森氏菌广泛抑制宿主的先天免疫应答，但尚不清楚确切地需要抑制哪些信号以建立感染的炎症前阶段。在这里，我们表明，早期血小板活化因子介导的抑制白细胞介素-17（IL-17）在肺泡巨噬细胞和肺中性粒细胞的表达限制中性粒细胞迁移到肺部，并有助于建立一个炎症前阶段的疾病。此外，IL-17最终有助于中性粒细胞迁移到气道，这定义了感染的后期促炎阶段。这些结果表明，IL-17的表达模式有助于原发性肺鼠疫的进展。
Inhalation of respiratory droplets infected with Yersinia pestis results in a rapidly progressing and lethal necrotic pneumonia called primary pneumonic plague. Disease manifests as biphasic, with an initial preinflammatory phase with rapid bacterial replication in the lungs absent readily detectable host immune responses. This is followed by the onset of a proinflammatory phase that sees the dramatic upregulation of proinflammatory cytokines and extensive neutrophil accumulation in the lungs. The plasminogen activator protease (Pla) is an essential virulence factor that is responsible for survival of Y. pestis in the lungs. Our lab recently showed that Pla functions as an adhesin that promotes binding to alveolar macrophages to facilitate translocation of effector proteins called Yops into the cytosol of target host cells via a type 3 secretion system (T3SS). Loss of Pla-mediated adherence disrupted the preinflammatory phase of disease and resulted in early neutrophil migration to the lungs. While it is established that Yersinia broadly suppresses host innate immune responses, it is not clear precisely which signals need to be inhibited to establish a preinflammatory stage of infection. Here, we show that early Pla-mediated suppression of Interleukin-17 (IL-17) expression in alveolar macrophages and pulmonary neutrophils limits neutrophil migration to the lungs and aids in establishing a preinflammatory phase of disease. In addition, IL-17 ultimately contributes to neutrophil migration to the airways that defines the later proinflammatory phase of infection. These results suggest that the pattern of IL-17 expression contributes to the progression of primary pneumonic plague.
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影响因子：
6.4
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Wan, Huanying