Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1.
Brucella control of dendritic cell maturation is dependent on the TIR-containing protein Btp1.
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DOI：
10.1371/journal.ppat.0040021
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发表时间：
2008-02-08
期刊：
影响因子：
6.7
通讯作者：
Gorvel, Jean-Pierre
中科院分区：
文献类型：
--
作者：
Salcedo, Suzana P.;Marchesini, Maria Ines;Lelouard, Hugues;Fugier, Emilie;Jolly, Gilles;Balor, Stephanie;Muller, Alexandre;Lapaque, Nicolas;Demaria, Olivier;Alexopoulou, Lena;Comerci, Diego J.;Ugalde, Rodolfo A.;Pierre, Philippe;Gorvel, Jean-Pierre
布鲁氏菌是一种细胞内病原体，能够在宿主体内持续很长一段时间并形成慢性病。我们发现，在布鲁氏菌接种肠环后不久，来自回肠Peyer‘s斑块的树突状细胞被感染，并构成这种病原体的细胞靶点。在体外，我们发现布鲁氏菌在树突状细胞内复制并阻碍其功能激活。此外，我们发现了一种新的布鲁氏菌蛋白Btp1，它通过干扰TLR2信号通路下调感染的树突状细胞的成熟。这些结果表明，细胞内的布鲁氏菌能够控制树突状细胞的功能，这可能在慢性布鲁氏菌病的发生发展中有重要的后果。细胞内致病菌引发传染病的一个关键决定因素是它们避免被宿主免疫系统识别的能力。尽管宿主细胞内的大多数微生物都得到了有效的清除，但布鲁氏菌的行为就像是一种特洛伊木马，会导致一种名为布鲁氏菌病的人畜共患病，对人类和动物都有影响。在这里，我们展示了致病性布鲁氏菌能够通过控制免疫系统的哨兵-树突状细胞的功能来靶向宿主细胞的防御机制。特别是，布鲁氏菌TIR蛋白(Btp1)针对Toll样受体2激活途径，这是参与细菌识别的主要宿主反应系统。Btp1参与抑制树突状细胞成熟。其直接后果是控制炎性细胞因子的分泌和T淋巴细胞的抗原呈递。这些细菌蛋白不是布鲁氏菌所特有的，已经在其他病原体中发现，可能是几种细胞内病原体用来诱发疾病的一般毒力机制的一部分。
Brucella is an intracellular pathogen able to persist for long periods of time within the host and establish a chronic disease. We show that soon after Brucella inoculation in intestinal loops, dendritic cells from ileal Peyer's patches become infected and constitute a cell target for this pathogen. In vitro, we found that Brucella replicates within dendritic cells and hinders their functional activation. In addition, we identified a new Brucella protein Btp1, which down-modulates maturation of infected dendritic cells by interfering with the TLR2 signaling pathway. These results show that intracellular Brucella is able to control dendritic cell function, which may have important consequences in the development of chronic brucellosis. A key determinant for intracellular pathogenic bacteria to induce infectious diseases is their ability to avoid recognition by the host immune system. Although most microorganisms internalized by host cells are efficiently cleared, Brucella behave as a Trojan horse causing a zoonosis called brucellosis that affects both humans and animals. Here we show that pathogenic Brucella are able to target host cell defense mechanisms by controlling the function of the sentinels of the immune system, the dendritic cells. In particular, the Brucella TIR-containing protein (Btp1) targets the Toll-like receptor 2 activation pathway, which is a major host response system involved in bacterial recognition. Btp1 is involved in the inhibition of dendritic cell maturation. The direct consequence is a control of inflammatory cytokine secretion and antigen presentation to T lymphocytes. These bacterial proteins are not specific for Brucella and have been identified in other pathogens and may be part of a general virulence mechanism used by several intracellular pathogens to induce disease.
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影响因子：
3.1
作者：
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通讯作者：
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影响因子：
15.3
作者：
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