Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei

• 成果类型: Article
• 署名作者: Beaver, Alexander K.; Keneskhanova, Zhibek; Cosentino, Raul 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.
• 署名单位: Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Bloomberg School of Public Health; University of Munich; University of Munich; Yale University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4783
• DOI: 10.1038/s41586-024-08151-z
• 发表日期: 2024-12-12
• 页码: 430-+
• 关键词: neisseria-gonorrhoeae; cd-hit; differentiation; generation; infection; responses; adhesion; protein; establishment; populations

摘要

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 genes(1-6). Recent studies of antigenic variation in vivo have focused near exclusively on parasites in the bloodstream(6-8), but research has shown that many, if not most, parasites reside in the interstitial spaces of tissues(9-13). We sought to explore the dynamics of antigenic variation in extravascular parasite populations using VSG-seq(7), 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.