Delineating dynamics of mucosal dendritic cell networks via intravital microscopy

Abstract

The gut associated lymphoid tissue maintains homeostasis with normal enteric flora while remaining primed to mount a protective response against pathogens. Recent studies have utilized genetic and intravital microscopic approaches to describe the role of dendritic cell (DC) subsets in protection from infectious microbes. In this study, we apply intravital microscopy to delineate mucosal DC dynamics. Using animals with a targeted replacement of a single allele of cx3cr1 with egfp, we visualize a single network of DCs spanning the superficial villus into deep lamina propria (LP). In small intestine, villus LP DCs overlap to form a meshwork of cells probing the microenvironment, similar to DCs in Peyer's Patch (PP) T cell zone. In deep LP, DCs form a network of circular structures, likely due to the presence of glands, with each unit comprised of 6 or fewer DCs. In large intestine, the network consists exclusively of circular structures. All DCs visualized are closely associated with vasculature. Interestingly, DC trafficking is not seen during homeostasis. Preliminary studies of T cell migration reveal that effector and regulatory T cells traffic along the same micro‐anatomic locale as the DC network. Together, this study highlights the extent and dynamic nature of the mucosal DC network and suggests the presence of a mucosal “highway” which facilitates interaction between DCs, effector T cells and regulatory T cells.