Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation

• Published in: European journal of immunology Vol. 50; no. 10; pp. 1525 - 1536
• Main Authors: Garcias López, Agnès, Bekiaris, Vasileios, Müller Luda, Katarzyna, Hütter, Julia, Ulmert, Isabel, Getachew Muleta, Konjit, Nakawesi, Joy, Kotarsky, Knut, Malissen, Bernard, O'Keeffe, Meredith, Holzmann, Bernhard, Winston Agace, William, Lahl, Katharina
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.10.2020; Wiley-VCH Verlag
• Subjects: Activation; Adaptive immunity; Animal models; Animals; Antigen presentation; Antigens; Basic Medicine; Cancer Vaccines; Cdc2 protein; Cell Movement; Cells, Cultured; Dendritic cells; Dendritic Cells - immunology; Drug development; Immunologi inom det medicinska området; Immunology; Immunology in the medical area; Interferon; Intestine; Intestines - immunology; Life Sciences; Lymph nodes; Lymphocyte Activation; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Inbred C57BL; Mice, Knockout; Migration; Pattern recognition receptors; Signal Transduction; TLR3; TLR3 protein; Toll-Like Receptor 3 - immunology; Toll-Like Receptor 3 - metabolism; Toll-like receptors; Tumor necrosis factor; Tumors; Type I interferon; Vaccination; Activation; Dendritic cells; Type I interferon; Migration; TLR3
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.201948497

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. Migration of dendritic cells to the draining lymph nodes is essential for the initiation of adaptive immunity. We show that migration of both subsets of dendritic cells in response to the dsRNA mimic poly(I:C) equally depends on TLR3, while type I IFN signaling is preferentially required by cDC1.