Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection.
Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection.
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DOI：
10.3389/fcimb.2021.689707
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发表时间：
2021
影响因子：
5.7
通讯作者：
Boutell C
中科院分区：
文献类型：
--
作者：
Charman M;McFarlane S;Wojtus JK;Sloan E;Dewar R;Leeming G;Al-Saadi M;Hunter L;Carroll MW;Stewart JP;Digard P;Hutchinson E;Boutell C
抗病毒效应蛋白的诱导作为对感染的稳态控制的先天免疫应答的一部分在限制呼吸道病原体的繁殖和传播中起关键作用。然而，这种免疫应答的长期诱导可导致肺过度炎症、组织损伤和呼吸衰竭。我们假设，暴露于持续感染威胁的组织可能组成性表达更高水平的抗病毒效应蛋白，以减少激活潜在有害的先天免疫防御的需要。通过分析来自一系列人体组织的转录组学数据，我们鉴定了肺组织相对于其他粘膜和非粘膜组织表达组成性更高水平的抗病毒效应基因。通过使用原代细胞系和恒河猴的气道，我们显示干扰素刺激的抗病毒效应蛋白TRIM22（三分基序22）在肺中独立于病毒感染或先天性免疫刺激组成型表达。这些发现与先前的报道形成对比，先前的报道显示TRIM22在实验室适应的细胞系中的表达需要干扰素刺激。我们证明TRIM22的组成性水平足以通过限制独立于干扰素介导的先天免疫防御的病毒转录的发作来抑制人和禽流感A病毒（IAV）感染的发作。因此，我们鉴定了TRIM22，以赋予来自呼吸道的细胞中针对IAV感染的预先存在的（内在的）细胞内防御。我们的数据突出了组织特异性和细胞类型依赖性模式的预先存在的免疫基因表达的IAV从感染开始的细胞内限制的重要性。
The induction of antiviral effector proteins as part of a homeostatically controlled innate immune response to infection plays a critical role in limiting the propagation and transmission of respiratory pathogens. However, the prolonged induction of this immune response can lead to lung hyperinflammation, tissue damage, and respiratory failure. We hypothesized that tissues exposed to the constant threat of infection may constitutively express higher levels of antiviral effector proteins to reduce the need to activate potentially harmful innate immune defences. By analysing transcriptomic data derived from a range of human tissues, we identify lung tissue to express constitutively higher levels of antiviral effector genes relative to that of other mucosal and non-mucosal tissues. By using primary cell lines and the airways of rhesus macaques, we show the interferon-stimulated antiviral effector protein TRIM22 (TRIpartite Motif 22) to be constitutively expressed in the lung independently of viral infection or innate immune stimulation. These findings contrast with previous reports that have shown TRIM22 expression in laboratory-adapted cell lines to require interferon stimulation. We demonstrate that constitutive levels of TRIM22 are sufficient to inhibit the onset of human and avian influenza A virus (IAV) infection by restricting the onset of viral transcription independently of interferon-mediated innate immune defences. Thus, we identify TRIM22 to confer a pre-existing (intrinsic) intracellular defence against IAV infection in cells derived from the respiratory tract. Our data highlight the importance of tissue-specific and cell-type dependent patterns of pre-existing immune gene expression in the intracellular restriction of IAV from the outset of infection.
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DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.7
作者：
Barr SD;Smiley JR;Bushman FD
通讯作者：
Bushman FD
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
5.4
作者：
Conn KL;Wasson P;McFarlane S;Tong L;Brown JR;Grant KG;Domingues P;Boutell C
通讯作者：
Boutell C
DOI：
10.1038/nrmicro3367
发表时间：
2015-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Eisfeld AJ;Neumann G;Kawaoka Y
通讯作者：
Kawaoka Y