Dynamic Interplay among Monocyte-Derived, Dermal, and Resident Lymph Node Dendritic Cells during the Generation of Vaccine Immunity to Fungi

Early innate events that enable priming of antifungal CD4 T cells are poorly understood. We engineered an attenuated fungal vaccine with a model epitope, E alpha RFP, to track vaccine immunity to Blastomyces dermatitidis during yeast recognition, antigen presentation, and priming of naive T cells. After subcutaneous injection of the vaccine, monocyte-derived inflammatory dendritic cells (DCs) are the earliest and largest population that associates with yeast, carrying them into the draining lymph nodes. Despite marked association with yeast, these DCs fail to display surface peptide:MHC complexes or prime naive T cells. Instead, the ability to display antigen and prime CD4 T cells resides with lymph node-resident DCs after antigen transfer from immigrant DCs and with skin migratory DCs. Our work reveals the dynamic interplay among distinct DC subsets that prime naive CD4 T cells after yeast are injected in the skin and discloses the cellular elements underlying vaccine-induced immunity to fungi.