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从感染到临床衣原体疾病的转变中,因果因素的相对贡献。

The relative contribution of causal factors in the transition from infection to clinical chlamydial disease.

机构信息

Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, 90 Sippy Downs Drive, Sippy Downs, Queensland, 4556, Australia.

School of Natural Sciences, University of Tasmania, Private Bag 55, Hobart, Tasmania, 7001, Australia.

出版信息

Sci Rep. 2018 Jun 11;8(1):8893. doi: 10.1038/s41598-018-27253-z.

DOI:10.1038/s41598-018-27253-z
PMID:29891934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5995861/
Abstract

Chlamydia is a major bacterial pathogen in humans and animals globally. Yet 80% of infections never progress to clinical disease. Decades of research have generated an interconnected network linking pathogen, host, and environmental factors to disease expression, but the relative importance of these and whether they account for disease progression remains unknown. To address this, we used structural equation modeling to evaluate putative factors likely to contribute to urogenital and ocular chlamydial disease in the koala (Phascolarctos cinereus). These factors include Chlamydia detection, load, and ompA genotype; urogenital and ocular microbiomes; host sex, age, weight, body condition; breading season, time of year; location; retrovirus co-infection; and major histocompatibility complex class II (MHCII) alleles. We show different microbiological processes underpin disease progression at urogenital and ocular sites. From each category of factors, urogenital disease was most strongly predicted by chlamydial PCR detection and load, koala body condition and environmental location. In contrast, ocular disease was most strongly predicted by phylum-level Chlamydiae microbiome proportions, sampling during breeding season and co-infection with koala retrovirus subtype B. Host MHCII alleles also contributed predictive power to both disease models. Our results also show considerable uncertainty remains, suggesting major causal mechanisms are yet to be discovered.

摘要

沙眼衣原体是一种主要的细菌病原体,在全球范围内影响人类和动物。然而,80%的感染从未发展为临床疾病。几十年来的研究已经生成了一个相互关联的网络,将病原体、宿主和环境因素与疾病表现联系起来,但这些因素的相对重要性以及它们是否导致疾病进展尚不清楚。为了解决这个问题,我们使用结构方程模型来评估可能导致考拉(Phascolarctos cinereus)泌尿生殖道和眼部衣原体疾病的假定因素。这些因素包括沙眼衣原体的检测、负荷和 ompA 基因型;泌尿生殖道和眼部微生物组;宿主的性别、年龄、体重、身体状况;繁殖季节、一年中的时间;位置;逆转录病毒合并感染;以及主要组织相容性复合体 II 类(MHCII)等位基因。我们展示了不同的微生物学过程,这些过程为泌尿生殖道和眼部疾病的进展提供了基础。在每个因素类别中,泌尿生殖道疾病最受沙眼衣原体 PCR 检测和负荷、考拉身体状况和环境位置的影响。相比之下,眼部疾病最受衣原体微生物组属水平比例、繁殖季节采样和考拉逆转录病毒亚型 B 合并感染的影响。宿主 MHCII 等位基因也为两种疾病模型提供了预测能力。我们的结果还表明,仍然存在很大的不确定性,这表明主要的因果机制尚未被发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf96/5995861/56fc69591e59/41598_2018_27253_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf96/5995861/0196670eb8b5/41598_2018_27253_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf96/5995861/0f618cb8c62f/41598_2018_27253_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf96/5995861/c001953f12b5/41598_2018_27253_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf96/5995861/56fc69591e59/41598_2018_27253_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf96/5995861/0196670eb8b5/41598_2018_27253_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf96/5995861/0f618cb8c62f/41598_2018_27253_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf96/5995861/c001953f12b5/41598_2018_27253_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf96/5995861/56fc69591e59/41598_2018_27253_Fig4_HTML.jpg

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