Chlamydia-induced ex vivo activation of B cells from mice, nonhuman primates, and humans produces large numbers of uniformly activated antigen presenting cells

Abstract

Chlamydia trachomatis (Ct) is a clinically important pathogen that causes ocular and genital infections. While genital Ct 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 Ct 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 ex vivo Chlamydia-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 Chlamydia-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 Chlamydia 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.