美国华盛顿大学医学院Chyi-Song Hsieh、L. David Sibley等研究人员合作发现，共生隐孢子虫定植引起cDC1依赖性Th1反应，从而促进肠道稳态并限制其他感染。这一研究成果于2021年10月28日在线发表在国际学术期刊《免疫》上。

研究人员揭示了在常规1型树突状细胞（cDC1）缺陷的小鼠患上隐孢子虫病时偶然发现的一种常见泰泽隐孢子虫（Ct-STL）免疫反应。Ct-STL在野生型小鼠中垂直传播，没有对健康产生负面影响。然而，Ct-STL引发了肠道免疫系统的深刻变化，包括诱导产生IFN-γ的Th1反应。TCR测序加上常见的Th1 TCR的体外和体内分析显示，Ct-STL引发了一个主要的抗原特异性Th1反应。

相反，cDC1的缺乏使Ct-STL的CD4 T细胞反应向Th17和调节性T细胞倾斜。尽管Ct-STL主要定植于小肠，但结肠Th1反应得到增强，并与防止鼠柠檬酸杆菌感染和葡聚糖硫酸钠及抗IL10R触发的结肠炎恶化有关。因此，Ct-STL代表了一种共生的病原体，能够引起Th1介导的肠道平衡，这可能反映了无症状人类中的隐孢子虫感染。

据悉，隐孢子虫可引起严重腹泻和发病，但许多感染是无症状的。

附：英文原文

Title: Commensal Cryptosporidium colonization elicits a cDC1-dependent Th1 response that promotes intestinal homeostasis and limits other infections

Author: Emilie V. Russler-Germain, Jisun Jung, Aidan T. Miller, Shannon Young, Jaeu Yi, Alec Wehmeier, Lindsey E. Fox, Kristen J. Monte, Jiani N. Chai, Devesha H. Kulkarni, Lisa J. Funkhouser-Jones, Georgia Wilke, Vivek Durai, Bernd H. Zinselmeyer, Rafael S. Czepielewski, Suellen Greco, Kenneth M. Murphy, Rodney D. Newberry, L. David Sibley, Chyi-Song Hsieh

Issue&Volume: 2021-10-28

Abstract: Cryptosporidium can cause severe diarrhea and morbidity, but many infections are asymptomatic. Here,we studied the immune response to a commensal strain of Cryptosporidium tyzzeri (Ct-STL) serendipitously discovered when conventional type 1 dendritic cell (cDC1)-deficientmice developed cryptosporidiosis. Ct-STL was vertically transmitted without negative health effects in wild-type mice.Yet, Ct-STL provoked profound changes in the intestinal immune system, including inductionof an IFN-γ-producing Th1 response. TCR sequencing coupled with in vitro and in vivo analysis of common Th1 TCRs revealed that Ct-STL elicited a dominant antigen-specific Th1 response. In contrast, deficiency incDC1s skewed the Ct-STL CD4 T cell response toward Th17 and regulatory T cells. Although Ct-STL predominantly colonized the small intestine, colon Th1 responses were enhancedand associated with protection against Citrobacter rodentium infection and exacerbation of dextran sodium sulfate and anti-IL10R-triggered colitis.Thus, Ct-STL represents a commensal pathobiont that elicits Th1-mediated intestinal homeostasisthat may reflect asymptomatic human Cryptosporidium infection.

DOI: 10.1016/j.immuni.2021.10.002

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00408-8