Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)/Universidad Católica de Córdoba (UCC), X5016HDK, Córdoba, Argentina.
Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina.
Nat Commun. 2023 May 3;14(1):2537. doi: 10.1038/s41467-023-38317-8.
The genomes of most protozoa encode families of variant surface antigens. In some parasitic microorganisms, it has been demonstrated that mutually exclusive changes in the expression of these antigens allow parasites to evade the host's immune response. It is widely assumed that antigenic variation in protozoan parasites is accomplished by the spontaneous appearance within the population of cells expressing antigenic variants that escape antibody-mediated cytotoxicity. Here we show, both in vitro and in animal infections, that antibodies to Variant-specific Surface Proteins (VSPs) of the intestinal parasite Giardia lamblia are not cytotoxic, inducing instead VSP clustering into liquid-ordered phase membrane microdomains that trigger a massive release of microvesicles carrying the original VSP and switch in expression to different VSPs by a calcium-dependent mechanism. This novel mechanism of surface antigen clearance throughout its release into microvesicles coupled to the stochastic induction of new phenotypic variants not only changes current paradigms of antigenic switching but also provides a new framework for understanding the course of protozoan infections as a host/parasite adaptive process.
大多数原生动物的基因组编码一系列变异表面抗原家族。在一些寄生微生物中，已经证明这些抗原表达的相互排斥变化使寄生虫能够逃避宿主的免疫反应。人们普遍认为，原生动物寄生虫的抗原变异是通过在表达逃避抗体介导的细胞毒性的抗原变异体的细胞群体中自发出现来实现的。在这里，我们在体外和动物感染中都表明，针对肠道寄生虫贾第虫的变体特异性表面蛋白 (VSP) 的抗体不是细胞毒性的，而是诱导 VSP 聚集到具有液有序相膜微区中，触发大量携带原始 VSP 的微泡释放，并通过钙依赖性机制切换到不同的 VSP 表达。这种通过释放到微泡中清除表面抗原的新机制与新表型变体的随机诱导相结合，不仅改变了抗原转换的当前范例，而且为理解原生动物感染作为宿主/寄生虫适应过程提供了一个新的框架。
