Effect of gonococcal lipooligosaccharide variation on human monocytic cytokine profile.
Effect of gonococcal lipooligosaccharide variation on human monocytic cytokine profile.
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DOI：
10.1186/1471-2180-7-7
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发表时间：
2007-01-26
期刊：
影响因子：
4.2
通讯作者：
Stein DC
中科院分区：
文献类型：
--
作者：
Patrone JB;Stein DC
淋病奈瑟氏菌是一种专性人类病原体，在世界范围内引起严重的发病率。N.淋病表达脂寡糖（LOS），一种在生物体发病过程中起重要作用的时相可变分子。淋球菌LOS结构的改变与疾病表现的改变相关。此外，LOS唾液酸化在体内容易发生，尽管这种唾液酸化在疾病期间的作用尚不清楚。用从表达不同结构定义的LOS的菌株中分离的纯化LOS制剂挑战人单核细胞，导致促炎细胞因子肿瘤坏死因子α（TNFα）和白细胞介素-12（IL-12）的产生相同。当单核细胞用表达这些LOS结构的活的或庆大霉素杀死的全细胞淋球菌变体挑战时，观察到类似的结果，尽管与纯化的LOS挑战相比观察到更大的细胞因子产生。用不同的LOS变体挑战人原代单核细胞模型，导致TNFα、IL-12、白细胞介素-10（IL-10）和白细胞介素-8（IL-8）的产生相似。采用细胞因子阵列以允许测量用淋球菌LOS变体以及表达唾液酸化LOS的变体激发的样品中的宽范围的细胞因子。与未唾液酸化淋球菌的挑战相比，用唾液酸化淋球菌挑战初级单核细胞显示出引起更多MCP-2（单核细胞趋化蛋白-2）的产生。我们证明，虽然在LOS的碳水化合物部分的改变不影响人类单核细胞的大多数细胞因子的生产，全细胞细菌的挑战是更具刺激性的挑战与纯化的LOS，这意味着其他淋球菌细胞表面抗原是重要的细胞因子的启发。与表达非唾液酸化LOS的淋球菌相比，表达唾液酸化LOS的淋球菌的挑战导致从挑战的细胞中诱导更多的趋化因子MCP-2。由于MCP-2是一种重要的化学引诱物，这表明唾液酸化可能在N.淋病
Neisseria gonorrhoeae is an obligate human pathogen that causes significant worldwide morbidity. N. gonorrhoeae expresses lipooligosaccharide (LOS), a phase variable molecule that plays an important role during pathogenesis of the organism. Alteration in the structure of gonococcal LOS correlates with altered disease presentation. In addition, LOS sialylation occurs readily in vivo, though the role of this sialylation during disease is unknown. Challenge of human monocytes with purified LOS preparations isolated from strains expressing distinct structurally defined LOSs resulted in identical production of the proinflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-12 (IL-12). Similar results were seen when monocytes were challenged with either live or gentamicin-killed whole cell gonococcal variants expressing these LOS structures, although greater cytokine production was observed in comparison with challenge by purified LOS. Challenge of a human primary monocyte model with distinct LOS variants resulted in similar production of TNFα, IL-12, interleukin-10 (IL-10), and interleukin-8 (IL-8). A cytokine array was employed to allow measurement of a broad range of cytokines in samples challenge with gonococcal LOS variants as well as variants expressing sialylated LOS. Challenge of primary monocytes with sialylated gonococci was shown to elicit the production of more MCP-2 (monocyte chemoattractant protein-2) in comparison with challenge by unsialylated gonococci. We demonstrated that while alterations in the carbohydrate moiety of LOS do not impact the production of most cytokines by human monocytes, whole-cell bacterial challenge is more stimulatory than challenge with purified LOS, implying that other gonococcal cell surface antigens are important for the elicitation of cytokines. Challenge with gonococci expressing sialylated LOS resulted in elicitation of more of the chemokine MCP-2 from challenged cells in comparison with gonococci expressing unsialylated LOS. As MCP-2 is an important chemoattractant, this indicates that in vivo sialylation may play an important role during the pathogenesis of N. gonorrhoeae.
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DOI：
10.1084/jem.186.2.247
发表时间：
1997-07-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Naumann M;Wessler S;Bartsch C;Wieland B;Meyer TF
通讯作者：
Meyer TF
影响因子：
6.4
作者：
Anzala, AO;Simonsen, JN;Plummer, FA
通讯作者：
Plummer, FA
影响因子：
5.5
作者：
Proost, P;Wuyts, A;VanDamme, J
通讯作者：
VanDamme, J
影响因子：
3.2
作者：
HITCHCOCK, PJ;BROWN, TM
通讯作者：
BROWN, TM
影响因子：
6.4
作者：
Braun, JM;Blackwell, CC;Beuth, J
通讯作者：
Beuth, J