title: Vibrio cholerae ghosts (VCG) exert immunomodulatory effect on dendritic cells for enhanced antigen presentation and induction of protective immunity.
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 marrow-derived 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 naïve 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 (UV-EBs). Furthermore, this interaction resulted in effective chlamydial antigen presentation to infection-sensitized but not naïve 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.
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA. feko@msm.edu.
authors.forename: Francis O
authors.initials: FO
authors.lastname: Eko
authors.affiliation: National Institute for Research in Reproductive Health, Mumbai, India. jayantimania@rediffmail.com.
authors.forename: Jayanti
authors.initials: J
authors.lastname: Mania-Pramanik
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA. rpais@msm.edu.
authors.forename: Roshan
authors.initials: R
authors.lastname: Pais
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA. panqing20050101@126.com.|College of Veterinary Medicine, China Agricultural University, Beijing, 100094, China. panqing20050101@126.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA. dan.okenu@transglobalconsults.com.
authors.forename: Daniel M N
authors.initials: DM
authors.lastname: Okenu
authors.affiliation: Clark Atlanta University, Atlanta, GA, USA. arieianjcau@gmail.com.
authors.forename: Arieian
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. cibegbu@rmy.emory.edu.
authors.forename: Chris
authors.initials: C
authors.lastname: Ibegbu
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing, 100094, China. hecheng@cau.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: He
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA. qhe@msm.edu.
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA. RRussell@msm.edu.
authors.forename: Raedeen
authors.initials: R
authors.lastname: Russell
authors.affiliation: Centers for Disease Control (CDC), Atlanta, GA, USA. cxb2@cdc.gov.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Black
authors.affiliation: Morehouse School of Medicine, Atlanta, GA, USA. jbi8@cdc.gov.|Centers for Disease Control (CDC), Atlanta, GA, USA. jbi8@cdc.gov.
authors.forename: Joseph U
authors.initials: JU
authors.lastname: Igietseme
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D002692:Chlamydia trachomatis / Q000737:chemistry / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D018417:Th1 Cells / Q000276:immunology*; D014734:Vibrio cholerae / Q000737:chemistry / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial