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疟原虫对胎盘的亚显微感染会导致哥伦比亚西北部女性出现Th1/Th2细胞因子失衡、炎症和缺氧。

Submicroscopic infection of placenta by Plasmodium produces Th1/Th2 cytokine imbalance, inflammation and hypoxia in women from north-west Colombia.

作者信息

Agudelo Olga M, Aristizabal Beatriz H, Yanow Stephanie K, Arango Eliana, Carmona-Fonseca Jaime, Maestre Amanda

机构信息

Grupo "Salud y Comunidad-César Uribe Piedrahita", Universidad de Antioquia, Medellin, Colombia.

出版信息

Malar J. 2014 Mar 27;13:122. doi: 10.1186/1475-2875-13-122.

Abstract

BACKGROUND

A large-scale study was set up in order to study the epidemiology, clinical aspects, and immunopathology of gestational and placental malaria in north-west Colombia. In this region, recent reports using a qPCR technique, confirmed frequencies of infection, by Plasmodium falciparum or Plasmodium vivax, up to 45%. Given the high rates of infection observed both in mother and placenta, a first exploratory study was proposed in order to characterize the effect on the inflammation status, tissue damage and hypoxia in Plasmodium spp. infected placentas.

METHODS

A descriptive, prospective, cross-sectional design was applied to pregnant women with (PM+) and without (PM-) placental malaria. Messenger RNA expression of Fas, FasL; COX-1, COX-2, HIF, VEGF, and the cytokines IL-2, IL-4, IL-10, IFN-γ and TNF, were measured in peripheral and placental blood using a quantitative PCR. The percentage of apoptotic cells was determined with a TUNEL assay.

RESULTS

In total 50 placentas were studied: 25 were positive for submicroscopic infection and 25 were negative for Plasmodium infection. Expression of IL-4 and IL-10 was observed high in placental tissue of PM+, while IL-2 was high in peripheral blood of the same group. Expression of TNF and IFNγ in peripheral blood of the PM + group was high. Similarly, the apoptotic index and Fas expression were significantly high in PM+. However, FasL expression was observed low in PM + compared to PM-. Inflammation markers (HIF, VEGF) and hypoxia markers (COX-1, COX-2) were high in the PM + group.

CONCLUSION

During placental malaria expression of some pro-inflammatory cytokines is up-regulated and markers of hypoxia and tissue damage are increased in cases of submicroscopic infection.

摘要

背景

开展了一项大规模研究,以研究哥伦比亚西北部妊娠期和胎盘疟疾的流行病学、临床特征及免疫病理学。在该地区,近期使用定量聚合酶链反应(qPCR)技术的报告证实,恶性疟原虫或间日疟原虫的感染率高达45%。鉴于在母亲和胎盘中均观察到高感染率,因此开展了一项初步探索性研究,以确定疟原虫感染的胎盘对炎症状态、组织损伤和缺氧的影响。

方法

对患有(PM+)和未患有(PM-)胎盘疟疾的孕妇采用描述性、前瞻性、横断面设计。使用定量PCR测定外周血和胎盘血中Fas、FasL、COX-1、COX-2、HIF、VEGF的信使核糖核酸(mRNA)表达以及细胞因子白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-10(IL-10)、干扰素-γ(IFN-γ)和肿瘤坏死因子(TNF)。采用末端脱氧核苷酸转移酶介导的缺口末端标记法(TUNEL法)测定凋亡细胞百分比。

结果

共研究了50个胎盘:25个亚显微镜感染呈阳性,25个疟原虫感染呈阴性。在PM+组的胎盘组织中,IL-4和IL-10的表达较高,而在同一组的外周血中,IL-2的表达较高。PM +组外周血中TNF和IFNγ的表达较高。同样,PM+组的凋亡指数和Fas表达显著升高。然而,与PM-组相比,PM +组中FasL表达较低。PM +组中炎症标志物(HIF、VEGF)和缺氧标志物(COX-1、COX-2)较高。

结论

在胎盘疟疾期间,亚显微镜感染时一些促炎细胞因子的表达上调,缺氧和组织损伤标志物增加。

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