Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
Department of Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin, China.
Mucosal Immunol. 2018 Jan;11(1):144-157. doi: 10.1038/mi.2017.20. Epub 2017 Mar 29.
Infection with the intestinal helminth parasite Heligmosomoides polygyrus exacerbates the colitis caused by the bacterial enteropathogen Citrobacter rodentium. To clarify the underlying mechanism, we analyzed fecal microbiota composition of control and helminth-infected mice and evaluated the functional role of compositional differences by microbiota transplantation experiments. Our results showed that infection of Balb/c mice with H. polygyrus resulted in significant changes in the composition of the gut microbiota, characterized by a marked increase in the abundance of Bacteroidetes and decreases in Firmicutes and Lactobacillales. Recipients of the gut microbiota from helminth-infected wide-type, but not STAT6-deficient, Balb/c donors had increased fecal pathogen shedding and significant worsening of Citrobacter-induced colitis compared to recipients of microbiota from control donors. Recipients of helminth-altered microbiota also displayed increased regulatory T cells and IL-10 expression. Depletion of CD4CD25 T cells and neutralization of IL-10 in recipients of helminth-altered microbiota led to reduced stool C. rodentium numbers and attenuated colitis. These results indicate that alteration of the gut microbiota is a significant contributor to the H. polygyrus-induced exacerbation of C. rodentium colitis. The helminth-induced alteration of the microbiota is Th2-dependent and acts by promoting regulatory T cells that suppress protective responses to bacterial enteropathogens.
感染肠道寄生虫旋毛虫会加剧由细菌病原体柠檬酸杆菌引起的结肠炎。为了阐明潜在的机制，我们分析了对照和感染旋毛虫的小鼠的粪便微生物群落组成，并通过微生物群落移植实验评估了组成差异的功能作用。我们的结果表明，感染 Balb/c 小鼠的旋毛虫导致肠道微生物群落组成发生显著变化，其特征是厚壁菌门的丰度显著增加，而 Firmicutes 和 Lactobacillales 的丰度降低。与从对照供体接受微生物群的受者相比，从感染旋毛虫的野生型（但不是 STAT6 缺陷型）Balb/c 供体接受微生物群的受者粪便病原体脱落增加，柠檬酸杆菌引起的结肠炎明显恶化。接受寄生虫改变的微生物群的受者还表现出增加的调节性 T 细胞和 IL-10 表达。在接受寄生虫改变的微生物群的受者中耗尽 CD4CD25 T 细胞和中和 IL-10 导致粪便 C. rodentium 数量减少和结肠炎减轻。这些结果表明，肠道微生物群落的改变是旋毛虫诱导的柠檬酸杆菌结肠炎恶化的一个重要因素。寄生虫诱导的微生物群改变是 Th2 依赖性的，通过促进调节性 T 细胞来发挥作用，抑制对细菌病原体的保护性反应。
