Characterization of Dendritic Cells Subpopulations in Skin and Afferent Lymph in the Swine Model

Abstract

Transcutaneous delivery of vaccines to specific skin dendritic cells (DC) subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC) and dermal DC (DDC) that could be divided in 3 subsets according to their phenotypes: (1) the CD163neg/CD172aneg, (2) the CD163highCD172apos and (3) the CD163lowCD172apos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163negCD172low DDC share properties with the CD8+ T cell response-inducing murine skin CD103pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC.

Aligning bona fide dendritic cell populations across species

“…In pig and macaques, cDC1 were the only cells to strongly express CADM1. In macaques, cDC1 were also XCR1 positive and expressed CLEC9A and BATF3 at the RNA level; similar to human cDC1, they also strongly expressed CD205 and CD162 and were responsive to TLR3 triggering [75,76]. cDC that closely resemble cDC1 in terms of FLT3, CADM1, CD205, TLR3 and XCR1 expression, were also identified for the first time in a non-mammalian species, the chicken [77].…”

“…Very recently, DC sharing phenotypic, molecular and functional similarities to mouse, human and sheep cDC1 were defined in other species including macaques, pigs and chickens [75,76]. In pig and macaques, cDC1 were the only cells to strongly express CADM1.…”

A Review of Histiocytic Diseases of Dogs and Cats

“…30 The scavenger receptors, CD163 and CD204, are also expressed by DC subsets in some species. 43,87 Expression patterns of CD163 and CD204 in normal canine DCs have not been reported. Of the markers mentioned, only CD11b is not assessable in formalin-fixed tissues.…”

“…5 Macrophage scavenger receptors are present on subsets of interstitial DCs, so this could be one potential point of reconciliation of the divergent data. 43,87 Also, dendritic cells are located in the meninges and choroid plexi but not in the brain. 19 Hence, the apparent site of initiation of CNS HS does have a resident population of interstitial DCs from which HS could develop.…”

Modified Vaccinia Virus Ankara-Based Vaccine Vectors Induce Apoptosis in Dendritic Cells Draining from the Skin via both the Extrinsic and Intrinsic Caspase Pathways, Preventing Efficient Antigen Presentation

“…Most systems used to investigate DC-T cell interactions rely on the isolation of monocytes or macrophages from blood or tissues (such as spleen or bone marrow) (63,71), followed by maturation with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) or the harvesting of tissues followed by isolation of resident DC. Only the model of cannulation of lymphatic vessels provides biological material, including DC derived from anatomical sites used in vaccination (31,32,34,49,68). Various DC models have been used to identify MVA-DC interactions to try to understand rMVA-induced immunogenicity.…”