小柯机器人

美国匹兹堡大学医学院Reinhard Hinterleitner研究团队发现，肠道原生生物Tritrichomonas (T.) arnold通过调节膳食抗原呈递树突状细胞(DC)抑制病毒介导的口服耐受性丧失(LOT)。相关论文于2023年7月20日发表于国际顶尖学术期刊《免疫》杂志上。

使用病毒介导的LOT小鼠模型，他们发现肠道定植的原生生物Tritrichomonas (T.) arnold促进口服耐受性，并保护免受呼肠孤病毒和小鼠norovirus介导的LOT，独立于微生物群。这种保护不是由于抗病毒宿主反应或T. arnold介导的先天2型免疫。从机制上讲，T. arnold直接抑制饮食中抗原呈递DC的促炎程序，随后限制T辅助性1 (Th1) 细胞并促进调节性T细胞反应。最后，粪便微生物组分析显示，在人类乳糜泻(CeD)患者中，T. arnold相关的副疟原虫菌株代表性不足。

总之，这些发现将激发进一步探索促进口腔耐受的原生蛋白在CeD和其他免疫介导的食物敏感性。

据悉，由DC启动谷蛋白特异性Th1细胞免疫反应驱动的对谷蛋白LOT是CeD的标志，可由肠道病毒感染引发。某些共栖物是否能调节病毒介导的LOT仍然是一个谜。

附：英文原文

Title: The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells

Author: Luzmariel Medina Sanchez, Magdalena Siller, Yanlin Zeng, Pamela H. Brigleb, Kishan A. Sangani, Ariadna S. Soto, Clarisse Engl, Colin R. Laughlin, Mohit Rana, Lauren Van Der Kraak, Surya P. Pandey, Mackenzie J. Bender, Britney Fitzgerald, Lee Hedden, Kay Fiske, Gwen M. Taylor, Austin P. Wright, Isha D. Mehta, Syed A. Rahman, Heather J. Galipeau, Steven J. Mullett, Stacy L. Gelhaus, Simon C. Watkins, Premysl Bercik, Timothy J. Nice, Bana Jabri, Marlies Meisel, Jishnu Das, Terence S. Dermody, Elena F. Verdú, Reinhard Hinterleitner

Issue&Volume: 2023-07-20

Abstract: Loss of oral tolerance (LOT) to gluten, driven by dendritic cell (DC) priming of gluten-specificT helper 1 (Th1) cell immune responses, is a hallmark of celiac disease (CeD) andcan be triggered by enteric viral infections. Whether certain commensals can moderatevirus-mediated LOT remains elusive. Here, using a mouse model of virus-mediated LOT,we discovered that the gut-colonizing protist Tritrichomonas (T.) arnold promotes oral tolerance and protects against reovirus- and murine norovirus-mediatedLOT, independent of the microbiota. Protection was not attributable to antiviral hostresponses or T. arnold-mediated innate type 2 immunity. Mechanistically, T. arnold directly restrained the proinflammatory program in dietary antigen-presenting DCs,subsequently limiting Th1 and promoting regulatory T cell responses. Finally, analysisof fecal microbiomes showed that T. arnold-related Parabasalid strains are underrepresented in human CeD patients. Altogether, these findings willmotivate further exploration of oral-tolerance-promoting protists in CeD and otherimmune-mediated food sensitivities.

DOI: 10.1016/j.immuni.2023.06.022

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00279-0

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