Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation
Agnès Garcias López, Vasileios Bekiaris, Katarzyna M. Luda, Julia Hütter, Isabel Ulmert, Konjit Getachew Muleta, Joy Nakawesi, Knut Kotarsky, Bernard MALISSEN, Meredith O’Keeffe, Bernhard Holzmann, William W. Agace, Katharina Lahl
Abstract
Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.