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Chlamydia-infected macrophages are resistant to azithromycin treatment and are associated with chronic oviduct inflammation and hydrosalpinx development.
Immunology and Cell Biology ( IF 4 ) Pub Date : 2019-09-11 , DOI: 10.1111/imcb.12285
Marina Cg Harvie 1, 2 , Alison J Carey 1 , Charles W Armitage 1 , Connor P O'Meara 1 , Jesse Peet 1 , Zachary N Phillips 1 , Peter Timms 1, 3 , Kenneth W Beagley 1
Affiliation  

Chlamydia infection remains the leading sexually-transmitted bacterial infection worldwide, causing damaging sequelae such as tubal scarring, infertility and ectopic pregnancy. As infection is often asymptomatic, prevention via vaccination is the optimal strategy for disease control. Vaccination strategies aimed at preventing bacterial infection have shown some promise, although these strategies often fail to prevent damaging inflammatory pathology when Chlamydia is encountered. Using a murine model of Chlamydia muridarum genital infection, we employed two established independent models to compare immune responses underpinning pathologic development of genital Chlamydia infection. Model one uses antibiotic treatment during infection, with only early treatment preventing pathology. Model two uses a plasmid-cured variant strain of C. muridarum that does not cause pathologic outcomes like the plasmid-containing wild-type counterpart. Using these infection models, contrasted by the development of pathology, we identified an unexpected role for macrophages. We observed that mice showing signs of pathology had greater numbers of activated macrophages present in the oviducts. This may have been due to early differences in macrophage activation and proinflammatory signaling leading to persistent or enhanced infection. These results provide valuable insight into the cellular mechanisms driving pathology in Chlamydia infection and contribute to the design and development of more effective vaccine strategies for protection against the deleterious sequelae of Chlamydia infection of the female reproductive tract.

中文翻译:

衣原体感染的巨噬细胞对阿奇霉素治疗有抗性,并且与慢性输卵管炎症和输卵管积水有关。

衣原体感染仍然是全世界范围内主要的性传播细菌感染,引起破坏性后遗症,例如输卵管瘢痕形成,不孕和异位妊娠。由于感染通常是无症状的,因此通过疫苗预防是控制疾病的最佳策略。预防细菌感染的疫苗接种策略已显示出一定的希望,尽管当遇到衣原体时,这些策略通常无法防止破坏性炎症病理。使用鼠衣原体生殖器感染的鼠模型,我们采用了两个已建立的独立模型来比较支持生殖器衣原体感染病理发展的免疫反应。模型一在感染期间使用抗生素治疗,只有早期治疗才能预防病理。模型2使用质粒固化的C变异株。muridarum,不会引起病理结果,例如含有质粒的野生型对应物。使用这些感染模型,与病理学发展形成对比,我们确定了巨噬细胞的意外作用。我们观察到表现出病理迹象的小鼠在输卵管中存在大量活化的巨噬细胞。这可能是由于巨噬细胞活化和促炎信号转导的早期差异导致持续或增强的感染。这些结果为驱动衣原体感染病理的细胞机制提供了宝贵的见识,并有助于设计和开发更有效的疫苗策略,以保护女性生殖道衣原体感染的有害后遗症。
更新日期:2019-11-01
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