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P2X7 受体在脓毒症中诱导单核细胞线粒体功能障碍，并损害 NLRP3 炎性小体的激活。

P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis.

机构信息

Unidad de Inflamación Molecular y Cirugía Experimental, Instituto Murciano de Investigación Biosanitaria IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, 30120, Spain.

Unidad de Reanimación, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, 30120, Spain.

出版信息

Nat Commun. 2019 Jun 20;10(1):2711. doi: 10.1038/s41467-019-10626-x.

DOI:10.1038/s41467-019-10626-x
PMID:31221993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6586640/
Abstract

Sepsis is characterized by a systemic inflammatory response followed by immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection.

摘要

脓毒症的特征是全身炎症反应，随后宿主出现免疫抑制。代谢缺陷和线粒体功能衰竭在脓毒症免疫功能低下的患者中很常见。NLRP3 炎性小体在嘌呤能 P2X7 受体激活后建立炎症反应中很重要。在这里，我们研究了一组来源于腹腔感染的脓毒症患者，结果表明患者单核细胞中 P2X7 受体对 NLRP3 的激活受损。此外，大多数与脓毒症相关的死亡病例都存在 NLRP3 激活受到严重改变的患者。在脓毒症患者的单核细胞中，P2X7 受体与线粒体功能障碍有关。此外，P2X7 受体的激活会导致线粒体损伤，进而抑制 HIF-1α 对 NLRP3 的激活。我们在脓毒症的小鼠模型中证明，当 P2X7 受体在体内被激活时，死亡率会增加。这些数据揭示了一个由 P2X7 受体引发的分子机制，该机制在感染过程中导致 NLRP3 受损。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/59e3112c97ba/41467_2019_10626_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/14ce613a124f/41467_2019_10626_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/77af67699115/41467_2019_10626_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/d4725405e7cc/41467_2019_10626_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/413ae3530a7d/41467_2019_10626_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/b78a2544c577/41467_2019_10626_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/d2e925581095/41467_2019_10626_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/59e3112c97ba/41467_2019_10626_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/14ce613a124f/41467_2019_10626_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/77af67699115/41467_2019_10626_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/d4725405e7cc/41467_2019_10626_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/413ae3530a7d/41467_2019_10626_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/b78a2544c577/41467_2019_10626_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/d2e925581095/41467_2019_10626_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b222/6586640/59e3112c97ba/41467_2019_10626_Fig7_HTML.jpg

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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Guidelines for the use of flow cytometry and cell sorting in immunological studies.

Eur J Immunol. 2017-10

[2]
Caspase-11-mediated endothelial pyroptosis underlies endotoxemia-induced lung injury.

J Clin Invest. 2017-11-1

[3]
Understanding Immunosuppression after Sepsis.

Immunity. 2017-7-18

[4]
The P2X7 Receptor in Infection and Inflammation.

Immunity. 2017-7-18

[5]
Monocyte-Dependent Suppression of T-Cell Function in Postoperative Patients and Abdominal Sepsis.

Shock. 2017-12

[6]
Epidemiology and Changes in Mortality of Sepsis After the Implementation of Surviving Sepsis Campaign Guidelines.

J Intensive Care Med. 2017-6-26

[7]
P2X, P2X, and P2X Receptor Knock Out Mice Expose Differential Outcome of Sepsis Induced by α-Haemolysin Producing .

Front Cell Infect Microbiol. 2017-4-6

[8]
IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population.

Nat Commun. 2017-4-4

[9]
Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors.

Clin Exp Immunol. 2017-8

[10]
Deletion of Nlrp3 Augments Survival during Polymicrobial Sepsis by Decreasing Autophagy and Enhancing Phagocytosis.

J Immunol. 2017-2-1

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