Immunofibrogenic Gene Expression Patterns in Tanzanian Children with Ocular Chlamydia trachomatis Infection, Active Trachoma and Scarring: Baseline Results of a 4-Year Longitudinal Study.
Immunofibrogenic Gene Expression Patterns in Tanzanian Children with Ocular Chlamydia trachomatis Infection, Active Trachoma and Scarring: Baseline Results of a 4-Year Longitudinal Study.
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DOI：
10.3389/fcimb.2017.00406
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发表时间：
2017
影响因子：
5.7
通讯作者：
Burton MJ
中科院分区：
文献类型：
--
作者：
Ramadhani AM;Derrick T;Macleod D;Massae P;Mtuy T;Jeffries D;Roberts CH;Bailey RL;Mabey DCW;Holland MJ;Burton MJ
由沙眼衣原体引起的沙眼是世界上导致失明的主要传染性原因，并且仍然是一个重大的公共卫生问题。许多沙眼疾病的病理被认为是由宿主细胞和免疫反应间接引起的，然而，活动性沙眼期间的免疫反应以及这如何引发进行性瘢痕形成尚不清楚。定义对C的保护性与致病性免疫应答。沙眼衣原体对疫苗设计和评价很重要。本研究报告了坦桑尼亚儿童纵向队列的基线结果，这些儿童被监测了4年，以确定进行性瘢痕性沙眼的免疫纤维化和感染相关性。在该队列基线中，对506名6-10岁的儿童进行了临床体征、感染状态和91个感兴趣基因的表达评估，然后进行大规模阿奇霉素给药以控制沙眼。C.使用液滴数字PCR检测沙眼并使用定量实时PCR测量基因表达。毛囊、乳头状炎症和疤痕的患病率分别为33.6%、31.6%和28.5%。C.沙眼检出率为15.4%（78/506），其中62/78例有卵泡。C.沙眼感染与IFNG和IL 22的强烈上调、Th 1和NK细胞途径以及Th 17细胞相关细胞因子的富集有关。在没有感染的炎症个体中，IFNG/IL 22和NK细胞应答降低，然而，促炎因子、生长因子和基质因子仍然上调，粘蛋白下调。我们的数据表明，强烈的IFNG/IL 22反应，可能与Th 1和NK细胞的参与，是重要的清除C。感染后残留的促炎和促纤维化表型可能导致病理性瘢痕形成。有趣的是，女性似乎比男性更容易发生乳头状炎症和瘢痕形成，即使在这个年轻的年龄，尽管C水平相当。沙眼感染与男性相比，女性还增加了许多IFNγ途径相关基因的表达，这表明该途径在感染后的过度表达可能导致更严重的瘢痕形成。对这些因素的纵向研究将揭示它们对C.沙眼感染和疤痕并发症的发展。
Trachoma, caused by Chlamydia trachomatis, is the world's leading infectious cause of blindness and remains a significant public health problem. Much of trachomatous disease pathology is thought to be caused indirectly by host cellular and immune responses, however the immune response during active trachoma and how this initiates progressive scarring is not clearly understood. Defining protective vs. pathogenic immune response to C. trachomatis is important for vaccine design and evaluation. This study reports the baseline results of a longitudinal cohort of Tanzanian children, who were monitored for 4 years in order to determine the immunofibrogenic and infectious correlates of progressive scarring trachoma. In this cohort baseline, 506 children aged 6–10 years were assessed for clinical signs, infection status and the expression of 91 genes of interest prior to mass azithromycin administration for trachoma control. C. trachomatis was detected using droplet digital PCR and gene expression was measured using quantitative real-time PCR. The prevalence of follicles, papillary inflammation and scarring were 33.6, 31.6, and 28.5%, respectively. C. trachomatis was detected in 78/506 (15.4%) individuals, 62/78 of whom also had follicles. C. trachomatis infection was associated with a strong upregulation of IFNG and IL22, the enrichment of Th1 and NK cell pathways and Th17 cell-associated cytokines. In individuals with inflammation in the absence of infection the IFNG/IL22 and NK cell response was reduced, however, pro-inflammatory, growth and matrix factors remained upregulated and mucins were downregulated. Our data suggest that, strong IFNG/IL22 responses, probably related to Th1 and NK cell involvement, is important for clearance of C. trachomatis and that the residual pro-inflammatory and pro-fibrotic phenotype that persists after infection might contribute to pathological scarring. Interestingly, females appear more susceptible to developing papillary inflammation and scarring than males, even at this young age, despite comparable levels of C. trachomatis infection. Females also had increased expression of a number of IFNγ pathway related genes relative to males, suggesting that overexpression of this pathway in response to infection might contribute to more severe scarring. Longitudinal investigation of these factors will reveal their relative contributions to protection from C. trachomatis infection and development of scarring complications.
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影响因子：
3.7
作者：
Derrick T;Last AR;Burr SE;Roberts CH;Nabicassa M;Cassama E;Bailey RL;Mabey DC;Burton MJ;Holland MJ
通讯作者：
Holland MJ
影响因子：
7.2
作者：
Du Kun;Cheng Xiang-lin;Li Qi
通讯作者：
Li Qi
影响因子：
34.3
作者：
Bourne, Rupert R. A.;Stevens, Gretchen A.;Taylor, Hugh R.
通讯作者：
Taylor, Hugh R.
影响因子：
3.1
作者：
Frazer, Lauren C.;O'Connell, Catherine M.;Darville, Toni
通讯作者：
Darville, Toni
影响因子：
3.7
作者：
Chaurasia SS;Perera PR;Poh R;Lim RR;Wong TT;Mehta JS
通讯作者：
Mehta JS