美国约翰霍普金斯大学Monica R. Mugnier小组发现，组织间隙是布氏锥虫抗原多样性的储存库。这一研究成果于2024年10月30日在线发表在国际学术期刊《自然》上。

研究人员试图通过变异表面糖蛋白（VSG）-seq这一高通量测序方法，探讨血管外寄生虫群体中抗原变异的动态。研究人员发现，组织而非血液是针刺和采蚊叮咬引发的布氏锥虫感染中抗原多样性的主要储存库，超过75%的VSG仅存在于血管外空间。研究人员发现这种多样性的增加与组织空间中寄生虫清除速度较慢相关。

这些数据共同支持了一个模型，即在血管外空间中免疫反应较慢，为产生维持慢性感染所需的抗原多样性提供了更多时间。这些发现揭示了血管外空间在病原体多样化中的重要作用。

据了解，通过使用大量的VSG编码基因组库，原生动物寄生虫布氏锥虫通过其致密的VSG外壳的抗原变异来逃避宿主免疫系统的清除，并周期性地“切换”VSG的表达。近期关于体内抗原变异的研究几乎完全集中在血液中的寄生虫上，但研究表明许多寄生虫，甚至大多数寄生虫，存在于组织的间质空间中。

附：英文原文

Title: Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei

Author: Beaver, Alexander K., Keneskhanova, Zhibek, Cosentino, Ral O., Weiss, Brian L., Awuoche, Erick O., Smallenberger, Gretchen M., Buenconsejo, Gracyn Y., Crilly, Nathan P., Smith, Jaclyn E., Hakim, Jill M. C., Zhang, Bailin, Bobb, Bryce, Rijo-Ferreira, Filipa, Figueiredo, Luisa M., Aksoy, Serap, Siegel, T. Nicolai, Mugnier, Monica R.

Issue&Volume: 2024-10-30

Abstract: The protozoan parasite Trypanosoma brucei evades clearance by the host immune system through antigenic variation of its dense variant surface glycoprotein (VSG) coat, periodically ‘switching’ expression of the VSG using a large genomic repertoire of VSG-encoding genes1,2,3,4,5,6. Recent studies of antigenic variation in vivo have focused near exclusively on parasites in the bloodstream6,7,8, but research has shown that many, if not most, parasites reside in the interstitial spaces of tissues9,10,11,12,13. We sought to explore the dynamics of antigenic variation in extravascular parasite populations using VSG-seq7, a high-throughput sequencing approach for profiling VSGs expressed in populations of T. brucei. Here we show that tissues, not the blood, are the primary reservoir of antigenic diversity during both needle- and tsetse bite-initiated T. brucei infections, with more than 75% of VSGs found exclusively within extravascular spaces. We found that this increased diversity is correlated with slower parasite clearance in tissue spaces. Together, these data support a model in which the slower immune response in extravascular spaces provides more time to generate the antigenic diversity needed to maintain a chronic infection. Our findings reveal the important role that extravascular spaces can have in pathogen diversification.

DOI: 10.1038/s41586-024-08151-z

Source: https://www.nature.com/articles/s41586-024-08151-z