Deciphering the orchestration of fungal vaccine-induced CD8+ T cell responses by dendritic cells
Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B943
Abstract ID: 4756
Presenting Author:
Nitish A Kulkarni , Graduate Research Assistant at Univ. of Illinois, Urbana-Champaign
Abstract:
The global threat of fungal infections is alarming, especially in immunocompromised individuals, and a licensed vaccine is lacking. Dendritic cells are necessary for T cell responses, and their apt stimulation is necessary for vaccine success. The lymph node-resident conventional DC, cDC1, and cDC2, take up antigens from migratory DC (migDC) and induce CD8+ and CD4+ T-cell responses, respectively. However, monocyte-derived dendritic cells (moDCs) can modulate the ongoing T-cell responses under inflammation. Using a mouse model of subcutaneous fungal (Blastomyces dermatitidis) vaccination, we sought to determine the dynamics and kinetics of DC subsets in the presence and absence of CD4+ T cell help. The fungal vaccination increased the activation (CD80, CD86) and the number of XCR1+cDC1, SIRPa+cDC2, migDC1, migDC2, moDCs, and monocytes by day 5 post-vaccination and plateaued by day 8 before returning to basal levels by day 15 in the draining lymph nodes (dLN). Intriguingly, the presence of CD4+ T cells impaired migratory and moDC kinetics and activation (MHC-II, CD80, CD86) contrary to the existing paradigm. Notably, our in vitro experimental data suggested that the heat-killed vaccine strain alone could stimulate DCs better than the curdlan adjuvant and efficiently induce cytokine-producing CD8+ T cell responses. Thus, our study revealed the underlying mechanisms of DC kinetics and CD4 T cell-help requirements for developing efficacious fungal vaccine platforms.
Deciphering the orchestration of fungal vaccine-induced CD8+ T cell responses by dendritic cells
Category
Poster and Podium (Block Symposium)