Transient infection of the zebrafish notochord with E. coli induces chronic inflammation.
Transient infection of the zebrafish notochord with E. coli induces chronic inflammation.
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DOI：
10.1242/dmm.014498
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发表时间：
2014-07
影响因子：
4.3
通讯作者：
Lutfalla G
中科院分区：
文献类型：
--
作者：
Nguyen-Chi M;Phan QT;Gonzalez C;Dubremetz JF;Levraud JP;Lutfalla G
斑马鱼胚胎和幼体现在是研究传染病的成熟模型。非致病性革兰氏阴性大肠杆菌感染可诱导强烈且可重复的炎症反应。在这里，我们研究了斑马鱼幼虫的细胞反应时，E。大肠杆菌被注射到脊索中，并描述了效果。首先，我们提供了直接的证据，证明脊索是一个独特的器官，在炎症的早期阶段，白细胞（巨噬细胞和中性粒细胞）无法进入。第二，我们表明，脊索感染诱导宿主反应，其特征在于快速清除细菌，脊索周围强白细胞招募和细菌清除后持续数天的长期炎症。在这种炎症反应中，il1b首先在巨噬细胞中表达，随后在中性粒细胞中高水平表达。此外，敲低il1b改变了中性粒细胞向脊索的募集，证明了这种细胞因子在脊索炎症维持中的重要作用。最终，脊索的感染引起脊索的严重缺陷，这与该组织周围发生的中性粒细胞脱粒相关。这是第一个在体内的证据表明，中性粒细胞可以在没有直接遇到病原体的情况下去免疫。持续性炎症、中性粒细胞浸润和细胞外基质的重建是类似于骨感染和某些软骨病中所见的缺陷。由于脊索是一个短暂的胚胎结构，与软骨和骨密切相关，并有助于脊柱的形成，我们建议感染的脊索在斑马鱼幼虫作为一个新的模型来研究软骨和骨炎症的细胞和分子机制。
Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils) during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation.
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影响因子：
2.6
作者：
Gutierrez, K
通讯作者：
Gutierrez, K
影响因子：
3
作者：
Moon, MS
通讯作者：
Moon, MS
影响因子：
2.5
作者：
KIMMEL, CB;BALLARD, WW;SCHILLING, TF
通讯作者：
SCHILLING, TF
DOI：
10.1084/jem.164.6.2095
发表时间：
1986-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kupper TS;Ballard DW;Chua AO;McGuire JS;Flood PM;Horowitz MC;Langdon R;Lightfoot L;Gubler U
通讯作者：
Gubler U
影响因子：
4
作者：
Colucci-Guyon, Emma;Tinevez, Jean-Yves;Herbomel, Philippe
通讯作者：
Herbomel, Philippe