Specific Activation of Dendritic Cells Enhances Clearance of Bacillus anthracis following Infection

Dendritic cells are potent activators of the immune system and have a key role in linking innate and adaptive immune responses. In the current study we have used ex vivo pulsed bone marrow dendritic cells (BMDC) in a novel adoptive transfer strategy to protect against challenge with Bacillus anthracis, in a murine model. Pre-pulsing murine BMDC with either recombinant Protective Antigen (PA) or CpG significantly upregulated expression of the activation markers CD40, CD80, CD86 and MHC-II. Passive transfusion of mice with pulsed BMDC, concurrently with active immunisation with rPA in alum, significantly enhanced (p<0.001) PA-specific splenocyte responses seven days post-immunisation. Parallel studies using ex vivo DCs expanded from human peripheral blood and activated under the same conditions as the murine DC, demonstrated that human DCs had a PA dose-related significant increase in the markers CD40, CD80 and CCR7 and that the increases in CD40 and CD80 were maintained when the other activating components, CpG and HK B. anthracis were added to the rPA in culture. Mice vaccinated on a single occasion intra-muscularly with rPA and alum and concurrently transfused intra-dermally with pulsed BMDC, demonstrated 100% survival following lethal B. anthracis challenge and had significantly enhanced (p<0.05) bacterial clearance within 2 days, compared with mice vaccinated with rPA and alum alone.