Yeruva Laxmi, Bowlin Anne K, Spencer Nicole, Maurelli Anthony T, Rank Roger G
Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, USA.
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences and Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, USA.
Infect Immun. 2015 Aug;83(8):3176-83. doi: 10.1128/IAI.00532-15. Epub 2015 May 26.
An important question in the study of chlamydial genital tract disease is why some women develop severe upper tract disease while others have mild or even "silent" infections with or without pathology. Animal studies suggest that the pathological outcome of an infection is dependent upon both the composition of the infecting chlamydial population and the genotype of the host, along with host physiological effects, such as the cyclical production of reproductive hormones and even the size of the infecting inoculum or the number of repeated infections. In this study, we compared two variants of Chlamydia caviae, contrasting in virulence, with respect to their abilities to ascend the guinea pig genital tract. We then determined the effect of combining the two variants on the course of infection and on the bacterial loads of the two variants in the genital tract. Although the variants individually had similar infection kinetics in the cervix, SP6, the virulent variant, could be isolated from the oviducts more often and in greater numbers than the attenuated variant, AZ2. SP6 also elicited higher levels of interleukin 8 (IL-8) in the lower genital tract and increased leukocyte infiltration in the cervix and uterus compared to AZ2. When the two variants were combined in a mixed infection, SP6 outcompeted AZ2 in the lower genital tract; however, AZ2 was able to ascend the genital tract as readily as SP6. These data suggest that the ability of SP6 to elicit an inflammatory response in the lower genital tract facilitates the spread of both variants to the oviducts.
衣原体生殖道疾病研究中的一个重要问题是，为什么有些女性会发展为严重的上生殖道疾病，而另一些女性则有轻度甚至“无症状”感染，无论有无病理变化。动物研究表明，感染的病理结果取决于感染的衣原体群体组成、宿主基因型，以及宿主的生理效应，如生殖激素的周期性产生，甚至感染接种物的大小或重复感染的次数。在本研究中，我们比较了两种毒力不同的豚鼠衣原体变体在豚鼠生殖道上行方面的能力。然后，我们确定了将这两种变体组合在一起对感染过程以及生殖道中两种变体细菌载量的影响。尽管这两种变体在宫颈中的感染动力学相似，但与减毒株AZ2相比，强毒株SP6更常从输卵管中分离出来，且数量更多。与AZ2相比，SP6在下生殖道中还引发了更高水平的白细胞介素8（IL-8），并增加了宫颈和子宫中的白细胞浸润。当这两种变体在混合感染中组合时，SP6在下生殖道中胜过AZ2；然而，AZ2能够与SP6一样容易地上行至生殖道。这些数据表明，SP6在下生殖道中引发炎症反应的能力促进了两种变体向输卵管的传播。
