Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathways
Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathways
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DOI：
10.4049/jimmunol.169.7.3970
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发表时间：
2002-10-01
影响因子：
4.4
通讯作者：
Golenbock, DT
中科院分区：
文献类型：
--
作者：
Henneke, P;Takeuchi, O;Golenbock, DT
B族链球菌（GBS）强烈激活炎症反应。我们以前报道过，分泌的GBS“因子”通过Toll样受体（TLR）2和TLR 6激活吞噬细胞，但GBS细胞壁独立于这些受体激活细胞。我们假设，GBS的吞噬免疫功能，如炎症，摄取和消除细菌，发生通过协调的TLR，沿着协同受体CD 14和CD 11 b/CD 18。使用各种基因敲除小鼠，我们表明，GBS诱导的p38和NF-κ B的激活依赖于细胞质TLR衔接蛋白，髓样分化因子88（MyD 88）的表达，但不是TLR 2和/或TLR 4。CD 14和补体受体3缺失的巨噬细胞对全菌具有正常的细胞因子反应，尽管CD 14缺失细胞对GBS因子的反应被消除。杀菌氧物种的细胞内形成被证明是MyD 88依赖，然而，摄取GBS，细胞内杀死的O-2自由基的先决条件，发生独立的MyD 88。虽然补体受体3的缺失大大减少了调理GBS的摄取，但它并不影响杀菌O-2自由基或炎症信号中间体的形成。我们的结论是，炎症，杀菌和吞噬反应GBS发生通过平行的，但独立的过程。
Group B streptococci (GBS) vigorously activate inflammatory responses. We reported previously that a secreted GBS "factor" activates phagocytes via Toll-like receptor (TLR)2 and TLR6, but that GBS cell walls activate cells independently of these receptors. We hypothesized that the phagocytic immune functions in response to GBS, such as inflammation, uptake, and elimination of bacteria, occur through a coordinated engagement of TLRs, along with the coreceptors CD14 and CD11b/CD18. Using various knockout mice we show that GBS-induced activation of p38 and NF-kappaB depends upon the expression of the cytoplasmic TLR adapter protein, myeloid differentiation factor 88 (MyD88), but not TLR2 and/or TLR4. Macrophages with deletions of CD14 and complement receptor 3 had a normal cytokine response to whole bacteria, although the response to GBS factor was abrogated in CD14-null cells. The intracellular formation of bactericidal oxygen species proved to be MyD88 dependent; however, uptake of GBS, a prerequisite for intracellular killing by O-2 radicals, occurred independently of MyD88. While deletion of complement receptor 3 greatly diminished the uptake of opsonized GBS, it did not affect the formation of bactericidal O-2 radicals or inflammatory signaling intermediates. We conclude that the inflammatory, bactericidal, and phagocytic responses to GBS occur via parallel but independent processes.