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Helminth infections drive heterogeneity in human type 2 and regulatory cells.
Science Translational Medicine ( IF 15.8 ) Pub Date : 2020-01-01 , DOI: 10.1126/scitranslmed.aaw3703
Karin de Ruiter 1 , Simon P Jochems 1 , Dicky L Tahapary 1, 2, 3 , Koen A Stam 1 , Marion König 1 , Vincent van Unen 4 , Sandra Laban 4 , Thomas Höllt 5, 6 , Moustapha Mbow 7 , Boudewijn P F Lelieveldt 8, 9 , Frits Koning 4 , Erliyani Sartono 1 , Johannes W A Smit 10, 11 , Taniawati Supali 12 , Maria Yazdanbakhsh 1
Affiliation  

Helminth infections induce strong type 2 and regulatory responses, but the degree of heterogeneity of such cells is not well characterized. Using mass cytometry, we profiled these cells in Europeans and Indonesians not exposed to helminths and in Indonesians residing in rural areas infected with soil-transmitted helminths. To assign immune alteration to helminth infection, the profiling was performed before and 1 year after deworming. Very distinct signatures were found in Europeans and Indonesians, showing expanded frequencies of T helper 2 cells, particularly CD161+ cells and ILC2s in helminth-infected Indonesians, which was confirmed functionally through analysis of cytokine-producing cells. Besides ILC2s and CD4+ T cells, CD8+ T cells and γδ T cells in Indonesians produced type 2 cytokines. Regulatory T cells were also expanded in Indonesians, but only those expressing CTLA-4, and some coexpressed CD38, HLA-DR, ICOS, or CD161. CD11c+ B cells were found to be the main IL-10 producers among B cells in Indonesians, a subset that was almost absent in Europeans. A number of the distinct immune profiles were driven by helminths as the profiles reverted after clearance of helminth infections. Moreover, Indonesians with no helminth infections residing in an urban area showed immune profiles that resembled Europeans rather than rural Indonesians, which excludes a major role for ethnicity. Detailed insight into the human type 2 and regulatory networks could provide opportunities to target these cells for more precise interventions.

中文翻译:

蠕虫感染会导致人类2型和调控细胞异质性。

蠕虫感染可诱导强烈的2型和调节反应,但这类细胞的异质性程度尚未得到很好的表征。使用大规模流式细胞仪,我们在未接触蠕虫的欧洲人和印度尼西亚人以及居住在农村地区的被土壤传播的蠕虫感染的印度尼西亚人中对这些细胞进行了分析。为了将免疫改变分配给蠕虫感染,在驱虫之前和驱虫之后1年进行分析。在欧洲人和印度尼西亚人中发现了非常不同的特征,显示出蠕虫感染的印度尼西亚人中T辅助2细胞(尤其是CD161 +细胞和ILC2s)的频率增加,这在功能上通过对产生细胞因子的细胞的分析得到了证实。除了ILC2s和CD4 + T细胞外,印尼人的CD8 + T细胞和γδT细胞还产生2型细胞因子。调节性T细胞在印尼人中也得到了扩展,但只有那些表达CTLA-4的人,以及一些共表达CD38,HLA-DR,ICOS或CD161的人。发现CD11c + B细胞是印度尼西亚人B细胞中主要的IL-10产生者,而欧洲人中几乎没有该亚群。蠕虫感染清除后恢复原状,因此许多不同的免疫特征均由蠕虫驱动。此外,在城市中没有蠕虫感染的印度尼西亚人的免疫特征类似于欧洲人,而不是农村的印度尼西亚人,这排除了种族的主要作用。对人类2型和调控网络的详细了解可以为靶向这些细胞提供更精确的干预措施。发现CD11c + B细胞是印度尼西亚人B细胞中主要的IL-10产生者,而欧洲人中几乎没有该亚群。蠕虫感染清除后恢复原状,因此许多不同的免疫特征均由蠕虫驱动。此外,在城市中没有蠕虫感染的印度尼西亚人的免疫特征类似于欧洲人,而不是农村的印度尼西亚人,这排除了种族的主要作用。对人类2型和调控网络的详细了解可以为靶向这些细胞提供更精确的干预措施。发现CD11c + B细胞是印度尼西亚人B细胞中主要的IL-10产生者,而欧洲人中几乎没有该亚群。蠕虫感染清除后恢复原状,因此许多不同的免疫特征均由蠕虫驱动。此外,在城市中没有蠕虫感染的印度尼西亚人的免疫特征类似于欧洲人,而不是农村的印度尼西亚人,这排除了种族的主要作用。对人类2型和调控网络的详细了解可以为靶向这些细胞提供更精确的干预措施。居住在市区内没有蠕虫感染的印尼人的免疫特征类似于欧洲人,而不是印尼农村人,这排除了种族的主要作用。对人类2型和调控网络的详细了解可以为靶向这些细胞提供更精确的干预措施。居住在市区内没有蠕虫感染的印尼人的免疫特征类似于欧洲人,而不是印尼农村人,这排除了种族的主要作用。对人类2型和调控网络的详细了解可以为靶向这些细胞提供更精确的干预措施。
更新日期:2020-01-02
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