Dynamin inhibition interferes with inflammasome activation and cytokine gene expression in Streptococcus pyogenes‐infected human macrophages
Dynamin inhibition interferes with inflammasome activation and cytokine gene expression in Streptococcus pyogenes‐infected human macrophages
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Dynamin 抑制干扰化脓性链球菌感染的人巨噬细胞中炎症小体的激活和细胞因子基因的表达
DOI：
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发表时间：
2014
影响因子：
4.6
通讯作者：
I. Julkunen
中科院分区：
文献类型：
--
作者：
Sinikka Latvala;Satu Mäkelä;M. Miettinen;Emmanuelle Charpentier;I. Julkunen;I. Julkunen
在本研究中，我们分析了化脓性链球菌[A组链球菌（GAS）]激活人单核细胞源性巨噬细胞中NACHT-结构域-、富含亮氨酸重复序列-和含PYD蛋白3（NALP 3）炎性体复合物的能力，以及参与GAS诱导的炎症反应的分子和信号通路。我们重点分析了动力蛋白依赖性内吞作用的影响以及主要链球菌毒力因子链球菌溶血素O（SLO）和链球菌溶血素S（SLS）在GAS诱导的免疫应答中的作用。这些毒力因子通过在宿主细胞膜中形成孔参与免疫逃避，并帮助细菌从内体-溶酶体途径逃逸。我们分析了用活的或灭活的野生型GAS以及活的SLO和SLS缺陷型细菌刺激后人原代巨噬细胞中的细胞因子基因表达。细菌刺激后以剂量依赖性方式产生白细胞介素（IL）-1 β、IL-10、肿瘤坏死因子（TNF）-α和趋化因子（C-X-C基序）配体（CXCL）-10细胞因子，并且在活菌、灭活菌或突变菌之间未观察到细胞因子水平差异。这些数据表明，链球菌溶血素或其他分泌的细菌产物不是由GAS诱导的炎症反应所必需的。我们的数据表明，抑制巨噬细胞中的发动蛋白依赖性内吞作用可减弱IL-1β、TNF-α、干扰素（IFN）-β和CXCL-10 mRNA的诱导。我们还观察到，在细菌刺激后，pro-IL-1β蛋白被表达并通过炎性小体激活有效切割成成熟的IL-1β。此外，我们证明了多种信号通路参与了人巨噬细胞中GAS刺激的炎症反应。
In the present study, we have analysed the ability of Streptococcus pyogenes [Group A streptococcus (GAS)] to activate the NACHT‐domain‐, leucine‐rich repeat‐ and PYD‐containing protein 3 (NALP3) inflammasome complex in human monocyte‐derived macrophages and the molecules and signalling pathways involved in GAS‐induced inflammatory responses. We focused upon analysing the impact of dynamin‐dependent endocytosis and the role of major streptococcal virulence factors streptolysin O (SLO) and streptolysin S (SLS) in the immune responses induced by GAS. These virulence factors are involved in immune evasion by forming pores in host cell membranes, and aid the bacteria to escape from the endosome–lysosome pathway. We analysed cytokine gene expression in human primary macrophages after stimulation with live or inactivated wild‐type GAS as well as with live SLO and SLS defective bacteria. Interleukin (IL)‐1β, IL‐10, tumour necrosis factor (TNF)‐α and chemokine (C‐X‐C motif) ligand (CXCL)‐10 cytokines were produced after bacterial stimulation in a dose‐dependent manner and no differences in cytokine levels were seen between live, inactivated or mutant bacteria. These data suggest that streptolysins or other secreted bacterial products are not required for the inflammatory responses induced by GAS. Our data indicate that inhibition of dynamin‐dependent endocytosis in macrophages attenuates the induction of IL‐1β, TNF‐α, interferon (IFN)‐β and CXCL‐10 mRNAs. We also observed that pro‐IL‐1β protein was expressed and efficiently cleaved into mature‐IL‐1β via inflammasome activation after bacterial stimulation. Furthermore, we demonstrate that multiple signalling pathways are involved in GAS‐stimulated inflammatory responses in human macrophages.
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影响因子：
11.8
作者：
Macia, Eric;Ehrlich, Marcelo;Kirchhausen, Tomas
通讯作者：
Kirchhausen, Tomas
DOI：
10.1073/pnas.91.25.12115
发表时间：
1994-12-06
影响因子：
11.1
作者：
LAPENTA, D;RUBENS, C;CLEARY, PP
通讯作者：
CLEARY, PP
DOI：
10.1073/pnas.0408721102
发表时间：
2005-04-05
影响因子：
11.1
作者：
Håkansson, A;Bentley, CC;Wessels, MR
通讯作者：
Wessels, MR
影响因子：
20.3
作者：
Netea, Mihai G.;Nold-Petry, Claudia A.;Dinarello, Charles A.
通讯作者：
Dinarello, Charles A.
DOI：
10.1073/pnas.96.11.6261
发表时间：
1999-05-25
影响因子：
11.1
作者：
Coeshott, C;Ohnemus, C;Cheronis, J
通讯作者：
Cheronis, J