Immune Response and Microbiota Profiles during Coinfection with Plasmodium vivax and Soil-Transmitted Helminths.
Immune Response and Microbiota Profiles during Coinfection with Plasmodium vivax and Soil-Transmitted Helminths.
复制标题
DOI：
10.1128/mbio.01705-20
复制
发表时间：
2020-10-20
期刊：
影响因子：
6.4
通讯作者：
Loke P
中科院分区：
文献类型：
--
作者：
Easton AV;Raciny-Aleman M;Liu V;Ruan E;Marier C;Heguy A;Yasnot MF;Rodriguez A;Loke P
疟原虫（疟疾）和蠕虫寄生虫合并感染是常见的，这两种感染都可能受到宿主肠道微生物群的影响。然而，合并感染与肠道微生物群之间的关系尚不清楚。通过对哥伦比亚130名个体的血液/粪便样本进行全面分析，我们发现肠道微生物群与间日疟原虫（疟疾）寄生虫数量的关系可能比感染宿主的蠕虫寄生虫数量更密切。微生物群分析确定了间日疟原虫寄生虫负荷的更多预测因子，而血液样本分析确定了蠕虫寄生虫负荷的预测因子。这些结果是出乎意料的，因为我们预计每种寄生虫在其生物学生态位（血液为间日疟原虫，肠道为蠕虫）中具有更大的差异。相反，我们发现细菌分类群是间日疟原虫寄生虫血症水平的最强预测因子，而循环TGF-β水平是蠕虫寄生虫负荷的最强预测因子。肠道微生物群在土壤传播蠕虫（STH）和疟原虫共同感染期间的作用。是很难理解的。我们检测了130名个体的外周血和粪便样本，这些个体要么只感染间日疟原虫，要么同时感染间日疟原虫和STH，要么只感染STH，要么既不感染间日疟原虫也不感染STH。除了全血细胞计数（CBC）和分类计数外，还通过转录组测序（RNA-Seq）进行外周血样本的转录谱分析，通过16 S rRNA基因测序确定粪便微生物群落，并通过基于微珠的免疫测定法测量循环细胞因子水平。血细胞计数的差异，包括与中性粒细胞活化的转录特征相关的中性粒细胞百分比增加，主要由间日疟原虫感染驱动。间日疟原虫感染还与白细胞介素6（IL-6）、IL-8和IL-10水平升高相关;这些细胞因子水平不受STH合并感染的影响。令人惊讶的是，间日疟原虫感染与微生物群的差异比STH感染更密切相关。仅感染间日疟原虫的儿童表现出拟杆菌升高，普雷沃菌和梭菌水平降低，但在合并感染STH的个体中未观察到这些差异。我们还观察到间日疟原虫寄生虫血症在STH感染人群中较高。当我们使用机器学习来确定间日疟原虫寄生虫负担的最重要预测因素时（在间日疟原虫感染的个体中），细菌分类群是寄生虫血症的最强预测因素。相反，循环转化生长因子β（TGF-β）是鞭虫卵负荷的最强预测因子。这项研究提供了意想不到的证据，表明肠道微生物群与间日疟原虫的联系可能比与STH感染的联系更强。
Plasmodium (malaria) and helminth parasite coinfections are frequent, and both infections can be affected by the host gut microbiota. However, the relationship between coinfection and the gut microbiota is unclear. By performing comprehensive analyses on blood/stool samples from 130 individuals in Colombia, we found that the gut microbiota may have a stronger relationship with the number of P. vivax (malaria) parasites than with the number of helminth parasites infecting a host. Microbiota analysis identified more predictors of the P. vivax parasite burden, whereas analysis of blood samples identified predictors of the helminth parasite burden. These results were unexpected, because we expected each parasite to be associated with greater differences in its biological niche (blood for P. vivax and the intestine for helminths). Instead, we find that bacterial taxa were the strongest predictors of P. vivax parasitemia levels, while circulating TGF-β levels were the strongest predictor of helminth parasite burdens. The role of the gut microbiota during coinfection with soil-transmitted helminths (STH) and Plasmodium spp. is poorly understood. We examined peripheral blood and fecal samples from 130 individuals who were either infected with Plasmodium vivax only, coinfected with P. vivax and STH, infected with STH alone, or not infected with either P. vivax or STH. In addition to a complete blood count (CBC) with differential, transcriptional profiling of peripheral blood samples was performed by transcriptome sequencing (RNA-Seq), fecal microbial communities were determined by 16S rRNA gene sequencing, and circulating cytokine levels were measured by bead-based immunoassays. Differences in blood cell counts, including an increased percentage of neutrophils, associated with a transcriptional signature of neutrophil activation, were driven primarily by P. vivax infection. P. vivax infection was also associated with increased levels of interleukin 6 (IL-6), IL-8, and IL-10; these cytokine levels were not affected by STH coinfection. Surprisingly, P. vivax infection was more strongly associated with differences in the microbiota than STH infection. Children infected with only P. vivax exhibited elevated Bacteroides and reduced Prevotella and Clostridiaceae levels, but these differences were not observed in individuals coinfected with STH. We also observed that P. vivax parasitemia was higher in the STH-infected population. When we used machine learning to identify the most important predictors of the P. vivax parasite burden (among P. vivax-infected individuals), bacterial taxa were the strongest predictors of parasitemia. In contrast, circulating transforming growth factor β (TGF-β) was the strongest predictor of the Trichuris trichiura egg burden. This study provides unexpected evidence that the gut microbiota may have a stronger link with P. vivax than with STH infection.