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- Title
Vibrio cholerae ghosts (VCG) exert immunomodulatory effect on dendritic cells for enhanced antigen presentation and induction of protective immunity.
- Authors
Eko, Francis O.; Mania-Pramanik, Jayanti; Pais, Roshan; Qing Pan; Okenu, Daniel M. N.; Johnson, Arieian; Ibegbu, Chris; Cheng He; Qing He; Russell, Raedeen; Black, Carolyn M.; Igietseme, Joseph U
- Abstract
Background We previously showed that the Vibrio cholerae ghost platform (VCG; empty V. cholerae cell envelopes) is an effective delivery system for vaccine antigens promoting the induction of substantial immunity in the absence of external adjuvants. However, the mechanism by which these cell envelopes enhance immunity and stimulate a predominantly Th1 cellular and humoral immune response has not been elucidated. We hypothesized that the immunostimulatory ability of VCG involves dendritic cell (DC) activation. Objective The aims of this study were: a) to investigate the ability of DCs [using mouse bone marrowderived DCs (BMDCs) as a model system] to take up and internalize VCGs; b) to evaluate the immunomodulatory effect of internalized VCGs on DC activation and maturation and their functional capacity to present chlamydial antigen to na?ve and infection-sensitized CD4+ T cells and; c) to evaluate the ability of VCGs to enhance the protective immunity of a chlamydial antigen. Results VCGs were efficiently internalized by DCs without affecting their viability and modulated DC-mediated immune responses. VCG-pulsed DCs showed increased secretion of proinflammatory cytokines and expression of co-stimulatory molecules associated with DC maturation in response to stimulation with UV-irradiated chlamydial elementary bodies (UVEBs). Furthermore, this interaction resulted in effective chlamydial antigen presentation to infection-sensitized but not na?ve CD4+ T cells and enhancement of protective immunity. Conclusions The present study demonstrated that VCGs activate DCs leading to the surface expression of co-stimulatory molecules associated with DC activation and maturation and enhancement of protective immunity induced by a chlamydial antigen. The results indicate that the immunoenhancing activity of VCG for increased T-cell activation against antigens is mediated, at least in part, through DC triggering. Thus, VCGs could be harnessed as immunomodulators to target antigens to DCs for enhancement of protective immunity against microbial infections.
- Subjects
VIBRIO cholerae; CELL envelope (Biology); VACCINES; BONE marrow; IMMUNITY; CHLAMYDIA
- Publication
BMC Immunology, 2014, Vol 15, Issue 1, p1
- ISSN
1471-2172
- Publication type
Article
- DOI
10.1186/s12865-014-0056-x