Interleukin-8 induction by Burkholderia pseudomallei can occur without toll-like receptor signaling but requires a functional type III secretion system
Interleukin-8 induction by Burkholderia pseudomallei can occur without toll-like receptor signaling but requires a functional type III secretion system
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DOI：
10.1086/587905
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发表时间：
2008-06-01
影响因子：
6.4
通讯作者：
Gan, Yunn-Hwen
中科院分区：
文献类型：
--
作者：
Hii, Chung-Shii;Sun, Guang Wen;Gan, Yunn-Hwen
类鼻疽伯克霍尔德菌是类鼻疽病的病原体，类鼻疽是一种可导致无症状、慢性或急性疾病的传染病。在急性类鼻疽中，在器官和血液中发现高水平的促炎细胞因子和趋化因子，并且中性粒细胞在控制感染中起关键作用。我们展示了B。类鼻疽通过Toll样受体（TLR）2、TLR 4和TLR 5激活NF-κ B，但也可以激活NF-κ B并诱导白细胞介素（IL）-8而不涉及TLR。TLR非依赖性激活依赖于功能性Bsa III型分泌系统（T3 SS），并需要内化。p38和c-Jun N-末端激酶（JNK）的丝裂原活化蛋白激酶（MAPK）抑制剂严重损害了B诱导的IL-8。假鼻疽和减少的细菌内化。此外，T3 SS突变体比野生型细菌诱导更少的JNK磷酸化。因此，在没有或低表达TLR的细胞中，例如粘膜上皮细胞，B.类鼻疽可以通过NF-κ B和MAPK途径诱导IL-8，并得到Bsa T3 SS的辅助。
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease that can result in asymptomatic, chronic, or acute illness. In acute melioidosis, high levels of proinflammatory cytokines and chemokines are found in organs and blood, and neutrophils play a key role in controlling the infection. We showed that B. pseudomallei activates NF-kappa B via Toll-like receptor (TLR) 2, TLR4, and TLR5 but can also activate NF-kappa B and induce interleukin (IL)-8 without involving TLRs. TLR-independent activation depends on a functional Bsa type III secretion system (T3SS) and requires internalization. The mitogen-activated protein kinase(MAPK) inhibitors for p38 and c-Jun N-terminal kinase (JNK) severely impaired IL-8 induction by B. pseudomallei and reduced bacterial internalization. Furthermore, the T3SS mutant induced less JNK phosphorylation than did wild-type bacteria. Thus, in cells with no or low expression of TLRs, such as mucosal epithelial cells, B. pseudomallei can induce IL-8 via NF-kappa B and MAPK pathways, aided by Bsa T3SS.