Salmonella Typhimurium type III secretion effectors stimulate innate immune responses in cultured epithelial cells.
Salmonella Typhimurium type III secretion effectors stimulate innate immune responses in cultured epithelial cells.
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DOI：
10.1371/journal.ppat.1000538
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发表时间：
2009-08
期刊：
影响因子：
6.7
通讯作者：
Galán JE
中科院分区：
文献类型：
--
作者：
Bruno VM;Hannemann S;Lara-Tejero M;Flavell RA;Kleinstein SH;Galán JE
先天免疫受体对保守的细菌产物的识别导致炎症反应，控制病原体的传播，但也可能导致病理。肠上皮细胞暴露于细菌产物，因此必须阻止通过先天免疫受体的信号传导以避免病理。然而，肠道病原体能够刺激肠道炎症。我们在这里表明，肠道病原体鼠伤寒沙门氏菌可以通过不涉及先天免疫系统受体的机制刺激培养上皮细胞的先天免疫反应。相反，鼠伤寒沙门氏菌通过其III型分泌系统传递细菌效应蛋白SopE、SopE2和SopB来刺激这些反应，这些蛋白以冗余的方式刺激rho家族gtpase，导致丝裂原活化蛋白（MAP）激酶和NF-κB信号的激活。这些观察结果对了解鼠伤寒沙门氏菌诱导肠道炎症以及其他肠道炎症病理的机制具有重要意义。鼠伤寒沙门氏菌是美国食源性疾病最常见的原因之一，也是发展中国家腹泻疾病的主要原因。这种病原体通过刺激肠道炎症引起腹泻。本研究表明鼠伤寒沙门氏菌将分子传递到上皮细胞中，具有刺激促炎物质产生的能力。这一机制可能有助于病原体启动肠上皮的炎症反应。这项研究为鼠伤寒沙门氏菌引起腹泻的机制提供了见解。
Recognition of conserved bacterial products by innate immune receptors leads to inflammatory responses that control pathogen spread but that can also result in pathology. Intestinal epithelial cells are exposed to bacterial products and therefore must prevent signaling through innate immune receptors to avoid pathology. However, enteric pathogens are able to stimulate intestinal inflammation. We show here that the enteric pathogen Salmonella Typhimurium can stimulate innate immune responses in cultured epithelial cells by mechanisms that do not involve receptors of the innate immune system. Instead, S. Typhimurium stimulates these responses by delivering through its type III secretion system the bacterial effector proteins SopE, SopE2, and SopB, which in a redundant fashion stimulate Rho-family GTPases leading to the activation of mitogen-activated protein (MAP) kinase and NF-κB signaling. These observations have implications for the understanding of the mechanisms by which Salmonella Typhimurium induces intestinal inflammation as well as other intestinal inflammatory pathologies. Salmonella Typhimurium is one of the most common causes of food-borne illness in the United States and a major cause of diarrheal diseases in developing countries. This pathogen induces diarrhea by stimulating inflammation in the intestinal tract. This study shows that S. Typhimurium delivers molecules into epithelial cells with the capacity to stimulate the production of pro-inflammatory substances. This mechanism may help the pathogen to initiate the inflammatory response in the intestinal epithelium. This study provides insight into the mechanisms by which Salmonella Typhimurium causes diarrhea.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
30.5
作者：
Arbibe, L;Mira, JP;Knaus, UG
通讯作者：
Knaus, UG
影响因子：
3.1
作者：
ECKMANN, L;KAGNOFF, MF;FIERER, J
通讯作者：
FIERER, J
影响因子：
3.1
作者：
Barthel, M;Hapfelmeier, S;Hardt, WD
通讯作者：
Hardt, WD
影响因子：
4.8
作者：
Eckmann, L;Smith, JR;Kagnoff, MF
通讯作者：
Kagnoff, MF