CD11c+CD8α+ Dendritic Cells Promote Protective Immunity to Respiratory Infection with Bordetella pertussis

CD11c(+)CD8 alpha(+) and CD103(+) dendritic cells (DC) have been shown to promote regulatory T cell responses and mediate tolerance in the gastrointestinal tract. These cells have also been identified in the lung,, but their role in immunity to respiratory tract infection is not clear. In this study, we have used a murine model of infection with Bordetella pertussis to examine the function of DC subtypes in protective immunity in the lungs. We found a dramatic increase in the numbers of CD11c(+)CD8 alpha(+) DC in the cervical lymph nodes within 4 h of challenge with B. pertussis and these DC could acquire particulate Ag from the upper respiratory tract. CD11c(+)CD8 alpha(+) DC also infiltrated the lung with a peak 7 days after B. pertussis challenge. The infiltrating CD11c(+)CD8 alpha(+) DC expressed MHC, costimulatory and activation markers indicative of mature DC. The CD11c(+)CD8 alpha(+) DC in the cervical lymph nodes expressed IL-4 and IL-10 and lower levels of IFN-gamma, but in the lungs expressed predominantly IFN-gamma. Depletion of CD8 alpha(+) cells early in infection attenuated Th1 responses in the lungs and significantly reduced bacterial clearance. Conversely, transfer of FLT3 ligand (FL)-expanded CD11c(+)CD8 alpha(+) DC enhanced bacterial clearance, whereas GM-CSF-expanded conventional DC had no effect. The numbers of CD11c(+)CD8 alpha(+)CD103(+) cells were also increased during the early phase of infection. Blocking CD103 function caused a significant delay in bacterial clearance and a reduction in cellular infiltration into the lungs. These findings demonstrate that CD11c(+)CD8 alpha(+) and CD11c(+)CD103(+)DC play a protective role in mediating immunity to B. pertussis infection in the respiratory tract. The Journal of Immunology, 2009, 183: 400-410.