ASC and NLRP3 maintain innate immune homeostasis in the airway through an inflammasome-independent mechanism.,Mucosal Immunology

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ASC and NLRP3 maintain innate immune homeostasis in the airway through an inflammasome-independent mechanism.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-07-05 , DOI: 10.1038/s41385-019-0181-1
Rendong Fang _{1,

2} , Ryosuke Uchiyama _{3,

4} , Shunsuke Sakai _{2,

5} , Hideki Hara _{2,

6} , Hiroko Tsutsui ₃ , Takashi Suda ₇ , Masao Mitsuyama _{2,

8} , Ikuo Kawamura ₂ , Kohsuke Tsuchiya _{2,

7,

9}

Affiliation

It is widely accepted that inflammasomes protect the host from microbial pathogens by inducing inflammatory responses through caspase-1 activation. Here, we show that the inflammasome components ASC and NLRP3 are required for resistance to pneumococcal pneumonia, whereas caspase-1 and caspase-11 are dispensable. In the lung of S. pneumoniae-infected mice, ASC and NLRP3, but not caspase-1/11, were required for optimal expression of several mucosal innate immune proteins. Among them, TFF2 and intelectin-1 appeared to be protective against pneumococcal pneumonia. During infection, ASC and NLRP3 maintained the expression of the transcription factor SPDEF, which can facilitate the expression of the mucosal defense factor genes. Moreover, activation of STAT6, a key regulator of Spdef expression, depended on ASC and NLRP3. Overexpression of these inflammasome proteins sustained STAT6 phosphorylation induced by type 2 cytokines. Collectively, this study suggests that ASC and NLRP3 promote airway mucosal innate immunity by an inflammasome-independent mechanism involving the STAT6-SPDEF pathway.

中文翻译：

ASC 和 NLRP3 通过独立于炎性体的机制维持气道中的先天免疫稳态。

人们普遍认为，炎性体通过激活 caspase-1 诱导炎症反应来保护宿主免受微生物病原体的侵害。在这里，我们表明炎症小体成分 ASC 和 NLRP3 是抵抗肺炎球菌肺炎所必需的，而 caspase-1 和 caspase-11 是可有可无的。在肺炎链球菌感染小鼠的肺中，ASC 和 NLRP3（而非 caspase-1/11）是几种粘膜先天免疫蛋白的最佳表达所必需的。其中，TFF2 和 intelectin-1 似乎对肺炎球菌性肺炎具有保护作用。在感染过程中，ASC和NLRP3维持转录因子SPDEF的表达，可促进粘膜防御因子基因的表达。此外，激活 STAT6（Spdef 表达的关键调节因子）取决于 ASC 和 NLRP3。这些炎性体蛋白的过表达维持了 2 型细胞因子诱导的 STAT6 磷酸化。总的来说，这项研究表明 ASC 和 NLRP3 通过涉及 STAT6-SPDEF 通路的炎性体独立机制促进气道粘膜先天免疫。

更新日期：2019-11-18

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