Replication of Brucella melitensis inside primary human monocytes depends on mitogen activated protein kinase signaling
Replication of Brucella melitensis inside primary human monocytes depends on mitogen activated protein kinase signaling
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DOI：
10.1016/j.micinf.2013.04.007
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发表时间：
2013-06-01
影响因子：
5.8
通讯作者：
Paliogianni, Fotini
中科院分区：
文献类型：
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作者：
Dimitrakopoulos, Odyssefs;Liopeta, Kassiani;Paliogianni, Fotini
布鲁氏菌引起的感染的临床过程与其调节巨噬细胞的初始免疫应答以确保其细胞内复制的能力有关。与布鲁氏菌在人类细胞中存活有关的信号转导途径尚未完全阐明。我们在此研究了TLRMAPK依赖性信号通路参与布鲁氏菌在原代人单核细胞中的存活，使用活的羊种布鲁氏菌临床菌株。B。melitensis引起延迟的，TLR 2依赖的MAPK激活。p38（SB 203580）、ERK 1/2（PD 98059）和INK（SP 600125）的特异性MAPK抑制剂或抗TLR 2阻断Ab抑制以TNF-α、IL-6和IL-10产生为特征的炎症和抗炎反应。B的细胞内复制。Melitensis主要依赖于p38和JNK激活，而不受IL-10水平的影响。这是支持B存活的第一个证据。人单核细胞内的melitensis依赖于不同MAPK家族成员之间的相互作用，通过TLR 2激活，尽管最初的促炎反应。(c)2013年巴斯德研究所。由Elsevier Masson SAS出版。All rights reserved.
The clinical course of infections caused by Brucella is linked to its capacity to modulate the initial immune response of macrophages in order to ensure its intracellular replication. Signal transduction pathways implicated in the survival of Brucella in human cells are not completely elucidated. We herein investigated the involvement of the TLR MAPK-dependent signaling pathways in the survival of Brucella in primary human monocytes using live clinical strains of Brucella melitensis. B. melitensis caused a delayed, TLR2 dependent MAPK activation. Specific MAPK inhibitors for p38 (SB203580), ERK1/2 (PD98059) and INK (SP600125) or the anti-TLR2 blocking Ab inhibited both inflammatory and anti-inflammatory responses characterized by TNF-alpha, IL-6 and IL-10 production. Intracellular replication of B. melitensis was mainly dependent on p38 and JNK activation and not affected by IL-10 levels. These are the first evidence to support that survival of B. melitensis inside human monocytes depends on interplay among the different MAPK family members, activated through TLR2, in spite of an initial pro-inflammatory response. (c) 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.