PDF(Pubmed)
Abstract：
Diarrheal diseases are the second leading cause of death in children worldwide. Epidemiological studies show that co-infection with Giardia intestinalis decreases the severity of diarrhea. Here, we show that Giardia is highly prevalent in the stools of asymptomatic school-aged children. It orchestrates a Th2 mucosal immune response, characterized by increased antigen-specific Th2 cells, IL-25, Type 2-associated cytokines, and goblet cell hyperplasia. Giardia infection expanded IL-10-producing Th2 and GATA3+ Treg cells that promoted chronic carriage, parasite transmission, and conferred protection against Toxoplasma gondii-induced lethal ileitis and DSS-driven colitis by downregulating proinflammatory cytokines, decreasing Th1/Th17 cell frequency, and preventing collateral tissue damage. Protection was dependent on STAT6 signaling, as Giardia-infected STAT6-/- mice no longer regulated intestinal bystander inflammation. Our findings demonstrate that Giardia infection reshapes mucosal immunity toward a Type 2 response, which confers a mutualistic protection against inflammatory disease processes and identifies a critical role for protists in regulating mucosal defenses.
摘要：
腹泻病是全球儿童死亡的第二大原因。流行病学研究表明，与肠贾第鞭毛虫共感染可降低腹泻的严重程度。这里,我们表明,贾第虫在无症状学龄儿童的粪便中非常普遍.它协调Th2粘膜免疫反应，以抗原特异性Th2细胞增加为特征，IL-25，2型相关细胞因子，和杯状细胞增生。贾第虫感染扩大IL-10产生的Th2和GATA3+Treg细胞，促进慢性携带，寄生虫传播,并通过下调促炎细胞因子来赋予对弓形虫诱导的致死性回肠炎和DSS驱动的结肠炎的保护作用，降低Th1/Th17细胞频率，并防止附带组织损伤。保护依赖于STAT6信号，作为贾第虫感染的STAT6-/-小鼠不再调节肠道旁观者炎症。我们的发现表明，贾第虫感染重塑粘膜免疫对2型反应，它赋予了对炎症性疾病过程的共同保护，并确定了原生生物在调节粘膜防御方面的关键作用。
