Inhibition of interferon-γ-induced nitric oxide production in endotoxin-activated macrophages by cytolethal distending toxin
Inhibition of interferon-γ-induced nitric oxide production in endotoxin-activated macrophages by cytolethal distending toxin
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DOI：
10.1111/j.1399-302x.2008.00434.x
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发表时间：
2008-10-01
影响因子：
--
通讯作者：
Russo, M.
中科院分区：
文献类型：
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作者：
Fernandes, K. P. S.;Mayer, M. P. A.;Russo, M.
简介：细胞致死性膨胀毒素（CDT）是由某些致病性革兰氏阴性菌（如牙周致病微生物伴放线菌聚集杆菌）产生的DNA靶向剂。CDT靶向淋巴细胞和其他细胞，导致细胞周期停滞和细胞凋亡，损害宿主免疫应答，并导致由该微生物引起的感染持续存在。在这项研究中，我们探讨了CDT对先天性免疫反应的影响，通过调查它如何影响一氧化氮（NO）的生产由macrophages.Methods：小鼠腹腔巨噬细胞刺激大肠杆菌超声波和NO的生产进行了测量存在或不存在的活性CDT。我们观察到，CDT迅速和显着抑制诱导型一氧化氮合酶（iNOS）的NO产生的剂量依赖性的方式。结论：CDT的这种免疫抑制作用可能是CDT介导的免疫抑制的一个重要方面，对A.伴放线菌感染。
Introduction: Cytolethal distending toxin (CDT) is a DNA-targeting agent produced by certain pathogenic gram-negative bacteria such as the periodontopathogenic organism Aggregatibacter actinomycetemcomitans. CDT targets lymphocytes and other cells causing cell cycle arrest and apoptosis, impairing the host immune response and contributing to the persistence of infections caused by this microorganism. In this study we explored the effects of CDT on the innate immune response, by investigating how it affects production of nitric oxide (NO) by macrophages.Methods: Murine peritoneal macrophages were stimulated with Escherichia coli sonicates and NO production was measured in the presence or not of active CDT.Results: We observed that CDT promptly and significantly inhibited NO production by inducible nitric oxide synthase (iNOS) in a dose-dependent manner. This inhibition is directed towards interferon-gamma-dependent pathways and is not mediated by either interleukin-4 or interleukin-10.Conclusion: This mechanism may constitute an important aspect of the immunosuppression mediated by CDT and may have potential clinical implications in A. actinomycetemcomitans infections.