Serotonin and melatonin, neurohormones for homeostasis, as novel inhibitors of infections by the intracellular parasite chlamydia
Serotonin and melatonin, neurohormones for homeostasis, as novel inhibitors of infections by the intracellular parasite chlamydia
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DOI：
10.1093/jac/dki331
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发表时间：
2005-11-01
影响因子：
5.2
通讯作者：
Shirai, M
中科院分区：
文献类型：
--
作者：
Rahman, MA;Azuma, Y;Shirai, M
目的：衣原体是专性细胞内细菌，引起多种疾病，如肺炎、性传播疾病、结膜炎和人畜共患病。色氨酸耗损干扰素γ (ifn - γ)是宿主抵抗衣原体感染最重要的防御系统。因此，衣原体色氨酸代谢被认为在ifn - γ抗性、持续感染和宿主/组织趋性中起关键作用。我们测试了色氨酸衍生物对衣原体感染细胞的活性。方法：采用沙眼衣原体、肺炎衣原体和猫衣原体3种衣原体体外感染的方法，对色氨酸合成基因存在显著差异，对ifn - γ的敏感性不同的3种衣原体进行体外感染，评价衣原体的感染率和包涵体大小。结果：褪黑素和血清素被认为是维持生物体内平衡的神经激素，它们可以减少衣原体感染，但对其他细菌的生长没有作用。与ifn - γ不同，褪黑素限制了所有三种衣原体的感染，并且补充色氨酸不能恢复这种效果。褪黑素治疗宿主细胞可以减少感染，感染减少是中和百日咳毒素，G蛋白的抑制剂。褪黑素和血清素受体的配体也会阻碍感染。结论：褪黑素和血清素对衣原体感染的抑制机制与ifn - γ不同，可能涉及特异性g蛋白偶联受体。褪黑素被认为可以抑制衣原体发育周期的早期进展，如细胞内感染的建立和/或从初级体向网状体的转化。利用褪黑素、血清素或其衍生物可能有利于无害预防衣原体感染。
Objectives: Chlamydiae are obligate intracellular bacteria, causing a variety of diseases, i.e. pneumonia, sexually transmitted disease, conjunctivitis and zoonosis. Tryptophan depletion by interferon-gamma (IFN-gamma) is the most important host defence system against chlamydial infection. Thus chlamydial tryptophan metabolism is thought to play key roles for IFN-gamma resistance, persistent infection and host/tissue tropisms. We tested tryptophan derivatives for activity against chlamydia-infected cells.Methods: Rates of chlamydial infection and sizes of the inclusions were evaluated by in vitro infection using three Chlamydiaceae species, Chlamydia trachomatis, Chlamydophila pneumoniae and Chlamydophila felis, which show significant divergence of tryptophan synthesis genes and different susceptibilities to IFN-gamma.Results: Melatonin and serotonin, which are recognized as neural hormones for maintenance of organism homeostasis, reduced chlamydial infection but not other bacterial growth tested here. Unlike IFN-gamma, melatonin limited infection of all three chlamydiae and the effects were not recovered by tryptophan supplementation. Melatonin treatment only of host cells could diminish infection and the infection reduction was neutralized by a pertussis toxin, an inhibitor of G proteins. Ligands of melatonin and serotonin receptors also hampered infection.Conclusions: Inhibition mechanisms of chlamydial infection by melatonin and serotonin appear to be different from those of IFN-gamma and involve specific G-protein-coupled receptors. Melatonin is deemed to inhibit early progression of the chlamydial development cycle, such as establishment of intracellular infection and/or conversion from elementary body to reticulate body. Utilization of melatonin, serotonin or their derivatives may be advantageous for harmless prevention of chlamydial infection.