Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production.
Infection of Pro- and Anti-Inflammatory Macrophages by Wild Type and Vaccine Strains of Measles Virus: NLRP3 Inflammasome Activation Independent of Virus Production.
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DOI：
10.3390/v15020260
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发表时间：
2023-01-17
期刊：
影响因子：
--
通讯作者：
Griffin DE
中科院分区：
文献类型：
--
作者：
Suwanmanee S;Ghimire S;Edwards J;Griffin DE
在人类和非人类灵长类动物中，野生型麻疹病毒(WT)在淋巴组织中广泛复制，并诱导具有先天反应特征的NF-κB和炎性小体激活，而不需要I型干扰素。相比之下，减毒活疫苗(LAMV)在淋巴组织中的复制能力很差，体内几乎没有检测到细胞因子的产生。为了研究巨噬细胞对WT MeV和LAMV感染的先天反应，我们分析了原代人单核细胞来源的巨噬细胞和佛波醇肉豆蔻酸成熟的单核细胞THP-1细胞(M0)在MeV感染24小时后分化为炎性(M1)和抗炎(M2)表型。LAMV感染巨噬细胞比WT MeV更有效，但产生的病毒比WT MeV感染的巨噬细胞少。两种菌株均可诱导产生核因子-κ、B反应细胞因子IL-6和肿瘤坏死因子α，以及炎症体产物IL-1、β和IL-18，但均未出现下睑下垂。对缺失炎症体感受器结节样受体PYR3、干扰素-γ诱导蛋白16(IFI16)或黑色素瘤缺失(AIM)2的THP-1细胞的分析表明，IL-18的产生依赖于NLRP3、ASC和Caspase1。然而，M1细胞在没有ASC或Caspase1的情况下产生IL-1β，这表明在MeV诱导的前IL-1β处理中存在另一条途径。因此，巨噬细胞体外感染LAMV和WTMeV后的先天反应包括产生IL-6和肿瘤坏死因子α，以及激活NLRP3炎性小体释放IL-1β和IL-18。LAMV减毒会削弱传染性病毒的产生，但不会降低感染巨噬细胞的能力或对感染的先天反应。
In humans and non-human primates, wild type (WT) measles virus (MeV) replicates extensively in lymphoid tissue and induces an innate response characteristic of NF-κB and inflammasome activation without type I interferon. In contrast, the live attenuated MeV vaccine (LAMV) replicates poorly in lymphoid tissue with little detectable in vivo cytokine production. To characterize the innate responses of macrophages to WT MeV and LAMV infection, we analyzed primary human monocyte-derived macrophages and phorbol myristic acid-matured monocytic THP-1 cells (M0) polarized to inflammatory (M1) and anti-inflammatory (M2) phenotypes 24 h after MeV infection. LAMV infected macrophages more efficiently than WT MeV but produced less virus than WT MeV-infected macrophages. Both strains induced production of NF-κB-responsive cytokines IL-6 and TNFα and inflammasome products IL-1β and IL-18 without evidence of pyroptosis. Analysis of THP-1 cells deficient in inflammasome sensors NOD-like receptor pyrin (NLRP)3, IFN-γ-inducible protein 16 (IFI16) or absent in melanoma (AIM)2; adaptor apoptosis-associated speck-like protein containing a CARD (ASC) or effector caspase 1 showed that IL-18 production was dependent on NLRP3, ASC, and caspase 1. However, M1 cells produced IL-1β in the absence of ASC or caspase 1 indicating alternate pathways for MeV-induced pro-IL-1β processing. Therefore, the innate response to in vitro infection of macrophages with both LAMV and WT MeV includes production of IL-6 and TNFα and activation of the NLRP3 inflammasome to release IL-1β and IL-18. LAMV attenuation impairs production of infectious virus but does not reduce ability to infect macrophages or innate responses to infection.
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影响因子：
3.8
作者：
Andres, O;Obojes, K;Schneider-Schaulies, J
通讯作者：
Schneider-Schaulies, J
影响因子：
5.5
作者：
Kato, Seiichi;Ohgimoto, Shinji;Ogura, Hisashi
通讯作者：
Ogura, Hisashi
野生型麻疹病毒衰减独立于I型IFN。
影响因子：
4.8
作者：
Druelle, Johan;Sellin, Caroline I.;Waku-Kouomou, Diane;Horvat, Branka;Wild, Fabian T.
通讯作者：
Wild, Fabian T.
DOI：
10.1097/nen.0b013e31829a26b6
发表时间：
2013-07-01
影响因子：
3.2
作者：
Abdullah, Hani'ah;Brankin, Brenda;Cosby, Sara Louise
通讯作者：
Cosby, Sara Louise
影响因子：
5.4
作者：
de Vries, Rory D.;Lemon, Ken;Duprex, W. Paul
通讯作者：
Duprex, W. Paul