Murine Intestinal Neonatal and Adult Dendritic Cell Subset Migration and Activation Characteristics in Response to Toll-Like Receptor Stimulation Through MyD88.

Abstract

The initiation of adaptive immunity requires antigen presentation in immune inductive sites. Classical dendritic cells (cDC) sense peripheral immune response inducing cues and migrate to the tissue-draining lymph nodes upon engagement, where they present acquired antigen to cognate T cells. Vaccines include adjuvants, which enable cDC activation and migration, both essential steps in the cascade leading to adaptive immunity. We here show that the expression of MyD88, the adapter molecule downstream of most toll-like receptors (TLR), is essential for the migration of cDCs in response to several stimuli and that its restricted expression to the TLR-sensing cDC subset is sufficient for the migration of that subset. As efficacious oral vaccines are primarily needed for use in newborns, we further quantify and characterise neonatal intestinal cDCs in five-day-old mice and show that they follow the same rules and patterns as we identified for cDCs in the adult intestines. Together, our data suggest strong conservation of immune-inducing cues across ages and provide fundamental knowledge aiding adjuvant choice for neonatal vaccination strategies.