Activation of type III interferon genes by pathogenic bacteria in infected epithelial cells and mouse placenta.

Activation of type III interferon genes by pathogenic bacteria in infected epithelial cells and mouse placenta.
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DOI:
10.1371/journal.pone.0039080
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Cossart P
Cossart P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bierne H;Travier L;Mahlakõiv T;Tailleux L;Subtil A;Lebreton A;Paliwal A;Gicquel B;Staeheli P;Lecuit M;Cossart P

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细菌感染触发I型和II型干扰素基因的表达,但对它们对III型干扰素(IFN-λ)基因的影响知之甚少,III型干扰素(IFN-λ)基因的产物在上皮细胞抗病毒的先天免疫中起重要作用。在这里,我们研究了IFN-λ基因在培养的人上皮细胞感染不同的病原菌和小鼠胎盘感染李斯特菌的表达。我们首先发现,在肠LoVo细胞中,L.单核细胞增生需要细菌进入,并在感染的细菌细胞内阶段进一步增加。其他革兰氏阳性菌,金黄色葡萄球菌,表皮葡萄球菌和粪肠球菌,也诱导IFN-λ基因时,由LoVo细胞内化。相反,革兰氏阴性菌沙门氏菌、弗氏志贺菌和沙眼衣原体基本上不诱导IFN-λ。我们还发现IFN-λ基因在结核分枝杆菌感染的A549肺上皮细胞和L.单核细胞增多症。在人源化的胎儿胎盘绒毛膜增生症小鼠模型中,IFN-λ2/λ3 mRNA水平在感染L.单核细胞增多症。此外,胎儿胎盘组织对IFN-λ2有反应。总之,这些结果表明,IFN-λ可能是上皮组织中革兰氏阳性细胞内细菌免疫应答的重要调节剂。
Bacterial infections trigger the expression of type I and II interferon genes but little is known about their effect on type III interferon (IFN-λ) genes, whose products play important roles in epithelial innate immunity against viruses. Here, we studied the expression of IFN-λ genes in cultured human epithelial cells infected with different pathogenic bacteria and in the mouse placenta infected with Listeria monocytogenes. We first showed that in intestinal LoVo cells, induction of IFN-λ genes by L. monocytogenes required bacterial entry and increased further during the bacterial intracellular phase of infection. Other Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis, also induced IFN-λ genes when internalized by LoVo cells. In contrast, Gram-negative bacteria Salmonella enterica serovar Typhimurium, Shigella flexneri and Chlamydia trachomatis did not substantially induce IFN-λ. We also found that IFN-λ genes were up-regulated in A549 lung epithelial cells infected with Mycobacterium tuberculosis and in HepG2 hepatocytes and BeWo trophoblastic cells infected with L. monocytogenes. In a humanized mouse line permissive to fetoplacental listeriosis, IFN-λ2/λ3 mRNA levels were enhanced in placentas infected with L. monocytogenes. In addition, the feto-placental tissue was responsive to IFN-λ2. Together, these results suggest that IFN-λ may be an important modulator of the immune response to Gram-positive intracellular bacteria in epithelial tissues.
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