Participation of Necroptosis in the Host Response to Acute Bacterial Pneumonia.
Participation of Necroptosis in the Host Response to Acute Bacterial Pneumonia.
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DOI：
10.1159/000455100
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发表时间：
2017
影响因子：
5.3
通讯作者：
Prince A
中科院分区：
文献类型：
--
作者：
Ahn D;Prince A
常见的肺部病原体，如肺炎链球菌和金黄色葡萄球菌，以及负责医疗保健相关肺炎的宿主适应性病原体，如碳青霉烯耐药肺炎克雷伯菌和粘质沙雷氏菌，能够通过引起坏死性凋亡的RIPK 1/RIPK 3/MLKL级联激活细胞死亡。坏死性凋亡可通过多种机制影响肺炎的发病机制。该途径的激活可导致特定类型的免疫细胞（尤其是巨噬细胞）的损失，并且这样做通过其关键免疫调节功能的损失而促成宿主病理学。然而，在其他感染环境中，坏死性凋亡促进病原体清除和感染细胞的根除，以控制过度的促炎信号传导。细菌产生孔形成毒素提供了通过不同细菌物种激活坏死性凋亡的共同机制，具有取决于特定病原体的可变后果。本简要综述中包括的数据证明了碳青霉烯类耐药ST 258 K的能力。在肺炎的情况下，它们可以激活坏死性凋亡，这通过它们对CYLD表达的抑制来平衡。确切地说，坏死性凋亡和其他细胞死亡机制在对特定肺部病原体的反应中是如何共同调节的，仍然是一个积极研究的主题，并可能在未来提供潜在的治疗靶点。
Common pulmonary pathogens, such as Streptococcus pneumoniae and Staphylococcus aureus as well as the host-adapted pathogens responsible for health care associated pneumonias such as the carbapenem-resistant Klebsiella pneumoniae and Serratia marcesens are able to activate cell death through the RIPK1/RIPK3/MLKL cascade that causes necroptosis. Necroptosis can influence the pathogenesis of pneumonia through several mechanisms. Activation of this pathway can result in the loss of specific types of immune cells, especially macrophages and in doing so contribute to host pathology through loss of their critical immunoregulatory functions. However, in other settings of infection, necroptosis promotes pathogen removal and eradication of infected cells to control excessive proinflammatory signaling. Bacterial production of pore forming toxins provides a common mechanism to activate necroptosis by diverse bacterial species, with variable consequences depending upon the specific pathogen. Included in this brief review are data demonstrating the ability of the carbapenem-resistant ST258 K. pneumoniae to activate necroptosis in the setting of pneumonia, which is counterbalanced by their suppression of CYLD expression. Exactly how necroptosis and other mechanisms of cell death are co-regulated in the response to specific pulmonary pathogens remains a topic of active investigation and may provide potential therapeutic targets in the future.