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SARS-CoV-2 感染患者上呼吸道样本中固有免疫反应基因的表达:一项初步研究。

Expression of innate immune response genes in upper airway samples of SARS-CoV-2 infected patients: A preliminary study.

机构信息

ICMR-National Institute of Virology, Mumbai Unit, Indian Council of Medical Research, Haffkine Institute Campus, Mumbai, Maharashtra, India.

出版信息

Indian J Med Res. 2021 May;153(5&6):677-683. doi: 10.4103/ijmr.IJMR_131_21.

Abstract

BACKGROUND & OBJECTIVES: Upper respiratory mucosa is the entryway for SARS-CoV-2, and cells at this site form the first line of resistance against the pathogens. Innate immune response at this point is crucial for managing the replication and early stage symptoms of virus infection. This study was aimed to evaluate the expression of pattern recognition receptors and cytokines in upper airway cells of SARS-CoV-2 infected patients.

METHODS

Forty seven nasopharyngeal swab (NPS) specimens from 25 SARS-CoV-2 infected patients and 22 SARS-CoV-2 negative individuals were investigated for expression of toll-like receptors (TLRs), melanoma differentiation-associated protein 5 (MDA5), NOD-like receptors family pyrin domain containing 3 (NLRP3), angiotensin-converting enzyme 2 (ACE2), interleukin (IL) - 6, tumour necrosis factor alpha (TNFα) and type-1 interferons (IFNs) by real time reverse transcription polymerase chain reaction.

RESULTS

Increased expression of TLR2, MDA5 and ACE2 was detected in SARS-CoV-2 infected patients in comparison with controls. MDA5 expression was significantly higher in asymptomatic and mildly symptomatic SARS-CoV-2 positive patients than the patients with severe symptoms. The asymptomatic group showed significant induction of type 1 IFNs than the symptomatic group. Non-specific induction of TLR7 could be observed in nasopharyngeal (NP) cells irrespective of symptoms and SARS-CoV-2 positivity.

INTERPRETATION & CONCLUSIONS: The findings suggest that increased MDA5 in NP cells of asymptomatic SARS-CoV-2 positive patients may subsequently induce type 1 IFNs to protect the individuals from further clinical severity of SARS-CoV-2 infection. A future prospective study in NPS of larger cohort needs to be performed to confirm our findings.

摘要

背景与目的

上呼吸道黏膜是 SARS-CoV-2 的入口,该部位的细胞构成了抵抗病原体的第一道防线。此时的固有免疫反应对于控制病毒感染的复制和早期症状至关重要。本研究旨在评估 SARS-CoV-2 感染患者上呼吸道细胞中模式识别受体和细胞因子的表达。

方法

对 25 例 SARS-CoV-2 感染患者和 22 例 SARS-CoV-2 阴性个体的 47 份鼻咽拭子(NPS)标本进行了研究,采用实时逆转录聚合酶链反应检测 Toll 样受体(TLR)、黑色素瘤分化相关蛋白 5(MDA5)、核苷酸结合寡聚化结构域样受体家族富含pyrin 结构域 3(NLRP3)、血管紧张素转换酶 2(ACE2)、白细胞介素(IL)-6、肿瘤坏死因子-α(TNFα)和 1 型干扰素(IFNs)的表达。

结果

与对照组相比,SARS-CoV-2 感染患者的 TLR2、MDA5 和 ACE2 表达增加。无症状和轻度症状 SARS-CoV-2 阳性患者的 MDA5 表达明显高于症状严重的患者。无症状组的 1 型 IFN 诱导明显高于有症状组。无论症状和 SARS-CoV-2 阳性与否,均可观察到非特异性诱导的 TLR7 在 NP 细胞中的表达。

解释与结论

研究结果表明,无症状 SARS-CoV-2 阳性患者 NP 细胞中 MDA5 的增加可能随后诱导 1 型 IFNs,以保护个体免受 SARS-CoV-2 感染的进一步临床严重程度。需要在更大的队列中对 NPS 进行未来的前瞻性研究,以确认我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5835/8555587/0b5293e5e71c/IJMR-153-677-g001.jpg

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