Endotoxin tolerance and low activation of TLR-4/NF-κB axis in monocytes of COVID-19 patients.
Endotoxin tolerance and low activation of TLR-4/NF-κB axis in monocytes of COVID-19 patients.
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DOI：
10.1007/s00109-023-02283-x
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发表时间：
2023-02
影响因子：
4.7
通讯作者：
Romao, Pedro R. T.
中科院分区：
文献类型：
--
作者：
Dorneles, Gilson P.;Teixeira, Paula C.;Peres, Alessandra;Rodrigues Junior, Luiz Carlos;da Fonseca, Simone Goncalves;Monteiro, Marta Chagas;Eller, Sarah;Oliveira, Tiago F.;Wendland, Eliana M.;Romao, Pedro R. T.
循环中较高的内毒素可能表明严重COVID-19患者对合并感染的宿主免疫反应处于受损状态。我们评估了来自COVID-19患者的单核细胞在脂多糖（LPS）激发后的炎症反应。将健康对照、轻度COVID-19患者和重度COVID-19患者的全血样品与LPS孵育2小时。重度COVID-19患者血浆中LPS和sCD 14水平高于健康对照和轻度COVID-19患者。在非刺激的体外条件下，重度COVID-19患者的炎性细胞因子和PGE-2水平以及CD 14 + HLA-DR低单核细胞频率高于对照组。此外，与对照组相比，重度COVID-19患者在CD 14 + HLA-DR低水平中呈现出更高的NF-κB p65磷酸化，以及在CD 14 + HLA-DR高水平中TLR-4和NF-κB p65磷酸化的表达更高。与对照组相比，严重COVID-19患者全血中LPS的刺激导致细胞因子产生减少，但PGE-2水平升高。两种浓度的内毒素攻击均降低了重度COVID-19患者中CD 14 + HLA-DR低的频率，但与重度COVID-19组相比，健康对照和轻度COVID-19患者的CD 14+单核细胞中TLR-4表达和NF-κB p65磷酸化的增加更为明显。我们的结论是急性SARS-CoV-2感染与单核细胞内毒素反应减弱有关。 重症COVID-19患者的LPS和全身IL-6和TNF-α水平较高。严重的COVID-19患者表现出更高的CD 14 + HLA-DR低单核细胞。在严重COVID-19的单核细胞中发现TLR-4/NF-κB轴增加。严重COVID-19中全血LPS刺激后细胞因子的产生减弱。严重COVID-19中LPS刺激后单核细胞TLR-4/NF-κB活化降低。
Higher endotoxin in the circulation may indicate a compromised state of host immune response against coinfections in severe COVID-19 patients. We evaluated the inflammatory response of monocytes from COVID-19 patients after lipopolysaccharide (LPS) challenge. Whole blood samples of healthy controls, patients with mild COVID-19, and patients with severe COVID-19 were incubated with LPS for 2 h. Severe COVID-19 patients presented higher LPS and sCD14 levels in the plasma than healthy controls and mild COVID-19 patients. In non-stimulated in vitro condition, severe COVID-19 patients presented higher inflammatory cytokines and PGE-2 levels and CD14 + HLA-DRlow monocytes frequency than controls. Moreover, severe COVID-19 patients presented higher NF-κB p65 phosphorylation in CD14 + HLA-DRlow, as well as higher expression of TLR-4 and NF-κB p65 phosphorylation in CD14 + HLA-DRhigh compared to controls. The stimulation of LPS in whole blood of severe COVID-19 patients leads to lower cytokine production but higher PGE-2 levels compared to controls. Endotoxin challenge with both concentrations reduced the frequency of CD14 + HLA-DRlow in severe COVID-19 patients, but the increases in TLR-4 expression and NF-κB p65 phosphorylation were more pronounced in both CD14 + monocytes of healthy controls and mild COVID-19 patients compared to severe COVID-19 group. We conclude that acute SARS-CoV-2 infection is associated with diminished endotoxin response in monocytes. Severe COVID-19 patients had higher levels of LPS and systemic IL-6 and TNF-α. Severe COVID-19 patients presented higher CD14+HLA-DRlow monocytes. Increased TLR-4/NF-κB axis was identified in monocytes of severe COVID-19. Blunted production of cytokines after whole blood LPS stimulation in severe COVID-19. Lower TLR-4/NF-κB activation in monocytes after LPS stimulation in severe COVID-19.
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DOI：
10.1186/cc13110
发表时间：
2013-11-14
期刊：
Critical care (London, England)
影响因子：
--
作者：
López-Collazo E;del Fresno C
通讯作者：
del Fresno C
影响因子：
--
作者：
Blangy-Letheule A;Persello A;Michelland S;Cunin V;Souab F;Aillerie V;Dhot J;Erraud A;Montnach J;Seve M;Bourgoin-Voillard S;Rozec B;De Waard M;Lauzier B
通讯作者：
Lauzier B
影响因子：
4.4
作者：
Avendano-Ortiz, Jose;Lozano-Rodriguez, Roberto;Lopez-Collazo, Eduardo
通讯作者：
Lopez-Collazo, Eduardo
DOI：
10.1038/nri3552
发表时间：
2013-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/j.cmi.2020.07.041
发表时间：
2021-01
期刊：
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
影响因子：
--
作者：
Garcia-Vidal C;Sanjuan G;Moreno-García E;Puerta-Alcalde P;Garcia-Pouton N;Chumbita M;Fernandez-Pittol M;Pitart C;Inciarte A;Bodro M;Morata L;Ambrosioni J;Grafia I;Meira F;Macaya I;Cardozo C;Casals C;Tellez A;Castro P;Marco F;García F;Mensa J;Martínez JA;Soriano A;COVID-19 Researchers Group
通讯作者：
COVID-19 Researchers Group