IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis.
IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis.
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DOI：
10.1084/jem.20092265
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发表时间：
2010-06-07
期刊：
影响因子：
--
通讯作者：
Prasadarao NV
中科院分区：
文献类型：
--
作者：
Mittal R;Gonzalez-Gomez I;Panigrahy A;Goth K;Bonnet R;Prasadarao NV
抗生素在治疗新生儿大肠杆菌K1脑膜炎中的无效性和耐药性菌株的出现显然需要新的预防策略。我们观察到，在高度菌血症期间给予白细胞介素（IL）-10可清除对抗生素敏感和耐药的大肠杆菌。感染小鼠血液中的大肠杆菌。对感染动物大脑的显微CT研究显示，大体形态学变化与在感染的人类新生儿中观察到的相似。在小鼠中，IL-10，而不是抗生素或抗TNF抗体治疗预防由E.杆菌IL-10给药增加了感染小鼠的中性粒细胞和巨噬细胞中的CR3表达，而感染和未治疗的小鼠显示Fc γ RI和TLR 2表达增加。用IL-10预处理的中性粒细胞或巨噬细胞对E.与从野生型或IL-10 −/−小鼠中分离的细胞相比，当CR3在体内被siRNA敲低时，IL-10的保护作用被废除。吞噬细胞中CR3表达的增加是由于前列腺素E-2（PGE-2）水平的抑制引起的，而中性粒细胞和巨噬细胞中的前列腺素E-2水平在E.大肠杆菌感染。这些发现描述了IL-10介导的E.通过CR3转移细菌的进入和防止新生儿脑膜炎中PGE-2的形成来清除大肠杆菌。
Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcγRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10−/− mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10–mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis.
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影响因子：
--
作者：
Bedford, H;de Louvois, J;Harvey, D
通讯作者：
Harvey, D
炭疽致死的毒素介导的人和鼠树突状细胞杀死损害适应性免疫反应。
影响因子：
6.7
作者：
Alileche, Abdelkrim;Serfass, Evan R;Muehlbauer, Stefan M;Porcelli, Steven A;Brojatsch, Jurgen
通讯作者：
Brojatsch, Jurgen
DOI：
10.1111/j.1479-828x.2004.00304.x
发表时间：
2004-12-01
影响因子：
1.7
作者：
Jones, B;Peake, K;Battin, MR
通讯作者：
Battin, MR
影响因子：
15.9
作者：
Isberg, Ralph R.;Van Nhieu, Guy Tran
通讯作者：
Van Nhieu, Guy Tran
影响因子：
3.5
作者：
Ballok, DA;Woulfe, J;Sakic, B
通讯作者：
Sakic, B