Miguel Rodolfo D Vicetti, Charek Joseph G, Fan Shumin, Coble Dondrae, Calla Nirk E Quispe, Cherpes Thomas L
Department of Otolaryngology - Head and Neck Surgery, College of Medicine, The Ohio State University Wexner Medical Center, Columbus OH, USA.
University of Toledo College of Medicine and Life Sciences, Toledo OH, USA.
bioRxiv. 2025 Jul 31:2025.07.25.666778. doi: 10.1101/2025.07.25.666778.
() is a clinically important pathogen that causes ocular and genital infections. While genital infection in women is typically persistent and asymptomatic, the host responses that dampen inflammation while gradually eradicating this bacterium are only partially defined. Herein, we show that promotes human B cell activation via TLR2-mediated signaling of MyD88-dependent pathways and non-antigen-specific B cell receptor signaling that engages the CD19 and CD79a/b complex. We also found that -induced activation of B cells from the peripheral blood of humans or rhesus macaques (RM), or from murine splenocytes, generates cells with a phenotype characteristic of an activated antigen presenting cell (APC). Consistent with this phenotype, intravenous injection of -activated B cells (CAB) loaded with various cognate antigens (Ag) elicited robust Ag-specific T cell immunity in several experimental models. Specifically, RM injected with CAB loaded with a model Ag developed Ag-specific CD8 T cell immunity and mice injected with Ag-loaded CAB formed CD8 T cell immune responses that protected against virus challenge and tumor development. As nonspecifically activated B cells to form large numbers of uniformly activated APC readily loaded with cognate Ag, our studies suggest that CAB may offer foundation for a cellular vaccine platform that elicits robust Ag-specific CD8 T cell immunity against a variety of tumors and microbial pathogens.
(某病原体)是一种临床上重要的病原体,可引起眼部和生殖器感染。虽然女性的生殖器感染通常持续且无症状,但在逐渐根除这种细菌的同时抑制炎症的宿主反应仅得到部分定义。在此,我们表明该病原体通过Toll样受体2(TLR2)介导的髓样分化因子88(MyD88)依赖性途径信号传导以及与CD19和CD79a/b复合物结合的非抗原特异性B细胞受体信号传导来促进人类B细胞活化。我们还发现,该病原体诱导人类或恒河猴(RM)外周血中的B细胞活化,或诱导小鼠脾细胞活化,产生具有活化抗原呈递细胞(APC)表型特征的细胞。与此表型一致,在多个实验模型中,静脉注射负载各种同源抗原(Ag)的该病原体活化B细胞(CAB)可引发强大的抗原特异性T细胞免疫。具体而言,注射负载模型抗原的CAB的恒河猴产生了抗原特异性CD8 T细胞免疫,注射负载抗原的CAB的小鼠形成了可抵抗病毒攻击和肿瘤发展的CD8 T细胞免疫反应。由于该病原体可非特异性激活B细胞以形成大量均匀活化的APC,这些APC易于负载同源抗原,我们的研究表明,CAB可能为一种细胞疫苗平台提供基础,该平台可引发针对多种肿瘤和微生物病原体的强大抗原特异性CD8 T细胞免疫。