SARS-CoV-2, SARS-CoV-1, and HIV-1 derived ssRNA sequences activate the NLRP3 inflammasome in human macrophages through a non-classical pathway.
SARS-CoV-2, SARS-CoV-1, and HIV-1 derived ssRNA sequences activate the NLRP3 inflammasome in human macrophages through a non-classical pathway.
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DOI：
10.1016/j.isci.2021.102295
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发表时间：
2021-04-23
期刊：
影响因子：
5.8
通讯作者：
Spector SA
中科院分区：
文献类型：
--
作者：
Campbell GR;To RK;Hanna J;Spector SA
巨噬细胞通过释放促炎细胞因子，如IL-1β(IL-1β)、肿瘤坏死因子和IL-6，促进宿主对感染的早期反应。IL-1β的生物活性依赖于NLRP3炎性小体的激活，最终导致caspase-1的激活和下垂。最近的研究表明，NLRP3炎症小体激活在新冠肺炎和SARS的肺部炎症和纤维化中发挥了作用，并且有证据表明NLRP3参与了HIV-1疾病。在这里，我们证明了来自SARS-CoV-2、SARS-CoV-1和HIV-1的富含Gu的单链RNA(Gu-rich RNA)在没有下垂的情况下触发了人巨噬细胞TLR8依赖的促炎细胞因子反应，其中来自SARS-CoV-2刺突蛋白的富含Gu的RNA触发了最大的炎症反应。利用遗传和药物抑制，我们证明了成熟的IL-1β的诱导是通过依赖于caspase-1、caspase-8、NLRP3炎症体、钾外流和自噬的非经典途径，而不依赖于TRIF(TICAM 1)、维生素D3和焦下垂。富含GU的单链RNA通过TLR8诱导人巨噬细胞产生IL-1β、肿瘤坏死因子和IL-6 SARS-CoV-2RNA比SARS-CoV-1或HIV-1RNA诱导更大的炎症反应SARS-CoV-2RNA诱导TLR8介导的IL-1β的产生TLR8-介导的IL-1β的释放依赖于CASP8、K+外流、NLRP3和自噬免疫学；病毒学
Macrophages promote an early host response to infection by releasing pro-inflammatory cytokines such as interleukin-1β (IL-1β), TNF, and IL-6. The bioactivity of IL-1β is classically dependent on NLRP3 inflammasome activation, which culminates in caspase-1 activation and pyroptosis. Recent studies suggest a role for NLRP3 inflammasome activation in lung inflammation and fibrosis in both COVID-19 and SARS, and there is evidence of NLRP3 involvement in HIV-1 disease. Here, we show that GU-rich single-stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1, and HIV-1 trigger a TLR8-dependent pro-inflammatory cytokine response from human macrophages in the absence of pyroptosis, with GU-rich RNA from the SARS-CoV-2 spike protein triggering the greatest inflammatory response. Using genetic and pharmacological inhibition, we show that the induction of mature IL-1β is through a non-classical pathway dependent on caspase-1, caspase-8, the NLRP3 inflammasome, potassium efflux, and autophagy while being independent of TRIF (TICAM1), vitamin D3, and pyroptosis. GU-rich ssRNA induces IL-1β, TNF, and IL-6 from human macrophages through TLR8 SARS-CoV-2 RNA elicits a greater inflammatory response than SARS-CoV-1 or HIV-1 RNA SARS-CoV-2 RNA elicits TLR8-mediated IL-1β production in the absence of pyroptosis TLR8-mediated IL-1β release is dependent on CASP8, K+ efflux, NLRP3, and autophagy Immunology; Virology
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Toll样受体8配体激活维生素D介导的自噬反应，从而抑制人类免疫缺陷病毒1型。
影响因子：
6.7
作者：
Campbell GR;Spector SA
通讯作者：
Spector SA
形成孔的蛋白质加油D可以调节白细胞介素-1的巨噬细胞分泌。
影响因子：
32.4
作者：
Evavold CL;Ruan J;Tan Y;Xia S;Wu H;Kagan JC
通讯作者：
Kagan JC
影响因子：
8.7
作者：
Elliott EI;Sutterwala FS
通讯作者：
Sutterwala FS
DOI：
10.1016/s0140-6736(08)61113-7
发表时间：
2008-07-26
期刊：
Lancet (London, England)
影响因子：
--
作者：
Antiretroviral Therapy Cohort Collaboration
通讯作者：
Antiretroviral Therapy Cohort Collaboration
影响因子：
12.4
作者：
Conos, S. A.;Lawlor, K. E.;Lindqvist, L. M.
通讯作者：
Lindqvist, L. M.