Numerous studies have demonstrated that targeting antigens to FcγR can increase their immunogenicity and generate protective immune responses in various infection models. Previously, we have shown that targeting fixed Francisella tularensis bacteria to FcγRI and III in mice, via intranasal immunization with immune complexes, enhances specific immune responses that are protective against this pathogen. In this study we have utilized our F. tularensis model to dissect the "in vivo" cellular immune responses generated following FcγR targeting. Our results demonstrate for the first time that targeting fixed Francisella tularensis to FcγR: 1. increases the recruitment and activation of dendritic cells in the lungs of immunized mice, 2. increases the frequency and number of effector memory CD4+ T cells during F. tularensis infection in an IL-12-dependent manner, and 3. increases the frequency and number of IFN-γ producing effector memory T cells upon "in vitro" re-stimulation. These data, collectively, confirm the effectiveness of FcγR targeting as a vaccine strategy against infections with mucosal pathogens, and for the first time demonstrate the "in vivo" immunological mode of action involved in the observed protection.
- Copyright © 2013 by The American Association of Immunologists, Inc.