Laboratory of Cellular and Molecular Immunology, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Rua Sarmento Leite, Porto Alegre, RS, 245, 90050-170, Brazil.
Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.
J Mol Med (Berl). 2023 Feb;101(1-2):183-195. doi: 10.1007/s00109-023-02283-x. Epub 2023 Feb 15.
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-DR monocytes frequency than controls. Moreover, severe COVID-19 patients presented higher NF-κB p65 phosphorylation in CD14 + HLA-DR, as well as higher expression of TLR-4 and NF-κB p65 phosphorylation in CD14 + HLA-DR 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-DR 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. KEY MESSAGES: 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.
循环中更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受损。我们评估了 LPS 刺激后 COVID-19 患者单核细胞的炎症反应。将健康对照者、轻度 COVID-19 患者和严重 COVID-19 患者的全血样本与 LPS 孵育 2 小时。严重 COVID-19 患者的血浆内毒素和 sCD14 水平高于健康对照者和轻度 COVID-19 患者。在非刺激的体外条件下，严重 COVID-19 患者的炎症细胞因子和 PGE-2 水平以及 CD14+HLA-DR 单核细胞频率高于对照组。此外，严重 COVID-19 患者的 CD14+HLA-DR 中 NF-κB p65 磷酸化以及 CD14+HLA-DR 中 TLR-4 和 NF-κB p65 磷酸化的表达均高于对照组。与对照组相比，严重 COVID-19 患者全血 LPS 刺激导致细胞因子产生减少，但 PGE-2 水平升高。两种浓度的内毒素刺激均降低了严重 COVID-19 患者 CD14+HLA-DR 的频率，但与严重 COVID-19 组相比，健康对照者和轻度 COVID-19 患者的 CD14+单核细胞中 TLR-4 表达和 NF-κB p65 磷酸化的增加更为明显。我们得出结论，急性 SARS-CoV-2 感染与单核细胞对内毒素反应减弱有关。
严重 COVID-19 患者的 LPS 和全身 IL-6 和 TNF-α水平更高。严重 COVID-19 患者呈现更高的 CD14+HLA-DRlow 单核细胞。在严重 COVID-19 患者的单核细胞中鉴定出增加的 TLR-4/NF-κB 轴。严重 COVID-19 患者全血 LPS 刺激后细胞因子产生减少。严重 COVID-19 患者 LPS 刺激后单核细胞中 TLR-4/NF-κB 激活降低。
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