Differential Migration of Epidermal and Dermal Dendritic Cells during Skin Infection

Abstract

Dendritic cells (DCs) are extremely heterogeneous, most evident in the skin where a variety of different subsets have been identified in recent years. DCs of healthy skin include a number of distinct populations in the dermal layer as well as the well-characterized Langerhans cells (LCs) of the epidermis. These steady-state populations are augmented during bouts of local inflammation by additional monocyte-derived DCs. In an effort to better understand the distinction between the different subsets, we examined their behavior following skin infection with HSV. LC emigration rapidly followed appearance of virus in the skin and resulted in depopulation of regions in areas surrounding infected nerve endings. A separate DC population was found to accumulate within the dermis under patches of active epidermal infection with at least some derived from blood monocyte precursors. Ag-positive DCs could occasionally be found in these dermal accumulations, although they represented a minority of DCs in these areas. In addition, infected DCs appeared compromised in their trafficking capabilities and were largely absent from the migrating population. On resolution of skin disease, LCs repopulated the reformed epidermis and these were of mixed origin, with around half entering from the circulation and the remainder derived from local progenitors. Overall, our results show a range of migrational complexities between distinct skin DC populations as a consequence of localized infection.

Herpes Simplex Virus Type 2–Infected Dendritic Cells Produce TNF-α, Which Enhances CCR5 Expression and Stimulates HIV Production from Adjacent Infected Cells

“…6. Studies in mice and humans suggest that the interaction of HSV-2-infected LCs with dermal DCs may both play a role in Ag processing and presentation to T cells (17,20,44,45). The sequence of these events is clear in mice (17) and recently was confirmed in humans (20).…”

“…Single-cell suspensions of these dermal infiltrates from skin biopsies supported HIV-1 superinfection in vitro (13). In mice, MDDCs generated in vivo also infiltrate herpetic lesions (45).…”

Early skin immunological disturbance after Plasmodium-infected mosquito bites

“…Our results showed that B cell percentages and CD11c + B220 + were very small and showed no difference amongst the groups (data not shown). The other APCs were divided in four groups, classified according to previous reports [18][19][20]: conventional/migrating DCs (cDCs/miDCs; CD11c high ), dermal/migrating DCs (DDCs/miDCs; CD11c low ), differentiating/migrating DCs (difDCs/miDCs; CD11c low CD11b + ), and monocytes/macrophages (monocytes/M0s; CD11b + ) ( Supplementary Fig. 4A), and an increase in the percentage of cDCs/miDCs in the skin of INF bite group was observed as compared to the control or NI bite groups (Fig.…”

Herpes Simplex Virus Infects Skin γδ T Cells before Langerhans Cells and Impedes Migration of Infected Langerhans Cells by Inducing Apoptosis and Blocking E-Cadherin Downregulation

“…+ dDCs from cultured murine skin Differences in the trafficking behavior of epidermal DCs and dDCs after zosteriform HSV infection of mice have been demonstrated using immunofluorescent microscopy of histological preparations of skin and by study of migration of HSV Ag + skin MDDCs to the draining LNs after s.c. injection (24). To precisely define the effect of HSV on skin DC subset emigration from skin after primary HSV infection, we applied wt HSV-2 virus or PBS to the tapestripped ears of mice and cultured the infected dorsal portion containing epidermis and dermis.…”

“…HSV is primarily a mucoepithelial infection, LCs are likely to be the first DCs to encounter HSV in the epidermis, but the kinetics of LC infection and the effect of virus on LC biology remains unclear. A recent immunohistological study of murine skin after zosteriform infection suggested that HSV induces differential migration of epidermal and dDCs but did not clearly distinguish between movement of individual skin DC subsets or clearly separate effects on migration of infected DCs from those on bystander, uninfected DCs (24). Furthermore, entry of virus to the skin was via retrograde spread from nerve endings, so the sequence of events after primary infection of keratinocytes was bypassed.…”