State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China; Department of Cariology and Endodontics, West China School of Stomatology, Sichuan University, Chengdu, China.
Department of Pathogenic Biology, Third Military Medical University, Chongqing, China.
Microbiol Res. 2022 May;258:126994. doi: 10.1016/j.micres.2022.126994. Epub 2022 Feb 19.
Malaria, caused by Plasmodium, is a global life-threatening infectious disease. However, the dynamic interactions between intestinal microbiota and host immunity during the infections are still unclear. Here, we investigated the change of intestinal microbiome and transcriptome during Plasmodium yoelii infection in mice. The mice were infected with P. yoelii through the intraperitoneal injection. The intestinal contents and tissues were collected at different time points along with the malaria procession and they were subjected to the microbiome and transcriptome sequencing and analysis respectively. The dynamic landscape of parasitemia-dependent intestinal microbiota and related host immunity were identified: (1) The diversity and composition of the intestinal microbiota represented a significant correlation with the Plasmodium infection; (2) Up-regulated genes from the intestinal transcriptome were mainly enriched in immune cell differentiation pathways, especially, naive CD4+ T cell differentiation to Th1/2 cells in the early immune response and Th17 cells in the later immune stage, T cell receptor (TCR) and B cell receptor (BCR) activation in the whole host immunity; (3) Host immune cells presented parasitemia phase-specific characteristics against P. yoelii infection; (4) There were significant associations between the parasitemia phase-specific microbiotas and the host immune response. Th1 cell differentiation was positively correlated with genera Moryella and specie Erysipelotrichaceae bacterium canine oral taxon 255, while negatively correlated with genera Ruminiclostridium. Th17 cell differentiation was related to the colonization of family Peptococcaceae, genera Lachnospiraceae FCS020 group, and specie Eubacterium plexicaudatum ASF492 and the reduction of family Bacteroidales BS11 gut group, genera Sutterella, and specie Parabacteroides distasonis str. 3776 D15 I. BCRs and TCRs were highly related with the family Bacteroidales BS11 gut group, genera Moryella, and specie Erysipelotrichaceae bacterium canine oral taxon 255, but negatively related with the genera Ruminiclostridium. Our results indicated a remarkable dynamic landscape and correlation of the parasitemia-dependent shifting of intestinal microbiota and immunity, suggesting the essential roles of intestinal microbiome on the modulation of host immunity against Plasmodium infection.
疟疾是由疟原虫引起的一种全球性的危及生命的传染病。然而，肠道微生物群与宿主免疫在感染过程中的动态相互作用仍不清楚。在这里，我们研究了 Plasmodium yoelii 感染小鼠时肠道微生物组和转录组的变化。通过腹腔注射将小鼠感染 P. yoelii。随着疟疾的进展，在不同时间点收集肠道内容物和组织，并分别进行微生物组和转录组测序和分析。确定了依赖于疟原虫血症的肠道微生物群和相关宿主免疫的动态景观：（1）肠道微生物群的多样性和组成与疟原虫感染呈显著相关；（2）肠道转录组上调的基因主要富集在免疫细胞分化途径中，特别是在早期免疫反应中幼稚 CD4+T 细胞向 Th1/2 细胞分化和后期免疫阶段向 Th17 细胞分化，整个宿主免疫中的 T 细胞受体（TCR）和 B 细胞受体（BCR）激活；（3）宿主免疫细胞针对 P. yoelii 感染呈现出与疟原虫血症阶段特异性的特征；（4）疟原虫血症阶段特异性微生物群与宿主免疫反应之间存在显著关联。Th1 细胞分化与属 Moryella 和种犬口腔分类群 255 的 Erysipelotrichaceae 细菌呈正相关，与属 Ruminiclostridium 呈负相关。Th17 细胞分化与科 Peptococcaceae、属 Lachnospiraceae FCS020 组和种 Eubacterium plexicaudatum ASF492 的定植以及科 Bacteroidales BS11 肠道组、属 Sutterella 和种 Parabacteroides distasonis str. 3776 D15 I 的减少有关。BCRs 和 TCRs 与科 Bacteroidales BS11 肠道组、属 Moryella 和种 Erysipelotrichaceae 细菌犬口腔分类群 255 高度相关，但与属 Ruminiclostridium 呈负相关。我们的结果表明，依赖于疟原虫血症的肠道微生物群和免疫的动态景观和相关性显著，表明肠道微生物组在调节宿主对疟原虫感染的免疫反应方面具有重要作用。
