Abstract:
Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to infant neurodevelopmental disabilities. An improved knowledge of correlates of protection against cCMV is needed to guide prevention strategies. Here, we employ an ex vivo model of human CMV (HCMV) infection in decidual tissues of women with and without preconception immunity against CMV, recapitulating nonprimary vs. primary infection at the authentic maternofetal transmission site. We show that decidual tissues of women with preconception immunity against CMV exhibit intrinsic resistance to HCMV, mounting a rapid activation of tissue-resident memory CD8+ and CD4+ T cells upon HCMV reinfection. We further reveal the role of HCMV-specific decidual-tissue-resident CD8+ T cells in local protection against nonprimary HCMV infection. The findings could inform the development of a vaccine against cCMV and provide insights for further studies of the integrity of immune defense against HCMV and other pathogens at the human maternal-fetal interface.
摘要:
先天性巨细胞病毒(cCMV)是最常见的宫内感染,导致婴儿神经发育障碍。需要对cCMV防护的相关知识进行改进,以指导预防策略。这里,我们采用人CMV(HCMV)感染的离体模型,在有和没有针对CMV的孕前免疫的妇女的蜕膜组织中,概述非原发性与原发感染在真正的母胎传播部位.我们表明,具有针对CMV的孕前免疫的女性的蜕膜组织表现出对HCMV的内在抗性,在HCMV再感染后,组织驻留记忆CD8+和CD4+T细胞的快速激活。我们进一步揭示了HCMV特异性蜕膜组织驻留CD8+T细胞在局部保护对抗非原发性HCMV感染中的作用。这些发现可以为针对cCMV的疫苗的开发提供信息,并为进一步研究人类母胎界面上针对HCMV和其他病原体的免疫防御的完整性提供见解。