Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for which there is no antiviral treatment and no vaccine. Macrophages are important in dengue pathogenesis; however, the initial target cell for DV infection remains unknown. As DV is introduced into human skin by mosquitoes of the genus Aedes, we undertook experiments to determine whether human dendritic cells (DCs) were permissive for the growth of DV. Initial experiments demonstrated that blood-derived DCs were 10-fold more permissive for DV infection than were monocytes or macrophages. We confirmed this with human skin DCs (Langerhans cells and dermal/interstitial DCs). Using cadaveric human skin explants, we exposed skin DCs to DV ex vivo. Of the human leukocyte antigen DR-positive DCs that migrated from the skin, emigrants from both dermis and epidermis, 60-80% expressed DV antigens. These observations were supported by histologic findings from the skin rash of a human subject who received an attenuated tetravalent dengue vaccine. Immunohistochemistry of the skin showed CD1a-positive DCs double-labeled with an antibody against DV envelope glycoprotein. These data demonstrate that human skin DCs are permissive for DV infection, and provide a potential mechanism for the transmission of DV into human skin.

Aim The laying of eggs and the building of a nest structure to accommodate them are two of the defining characteristics of members of the class Aves. Nest structures vary considerably across avian taxa and for many species the design of the completed nest can have important consequences for both parents and their offspring. While nest characteristics are expected to vary adaptively in response to environmental conditions, large-scale spatial variation in nest characteristics has been largely overlooked. Here, we examined the effects of latitudinal variation in spring temperatures on nest characteristics, including insulatory properties, and reproductive success of blue tits, Cyanistes caeruleus, and great tits, Parus major. \ud \ud Location Great Britain. \ud \ud Methods Nests and reproductive data were collected from seven study sites, spread over five degrees of latitude. Then, the nest insulatory properties were determined before the nests were separated into either nest base material or cup lining material. \ud \ud Results As spring temperatures increased with decreasing latitude, the mass of the nest base material did not vary in either species, whilst the mass of the cup lining material and nest insulatory properties decreased in both species. This suggests that in response to increasing temperatures the breeding female reduces the mass of the cup lining material thereby maintaining an appropriate microclimate for incubating and brooding. The mean laying dates of both species advanced with decreasing latitude and increasing spring temperatures, although reproductive success did not vary. \ud \ud Main conclusions This is the first study to demonstrate that birds are systematically adjusting their nest structure in response to variation in ambient temperatures across large spatial scales. Therefore, nest composition reliably indicates environmental conditions and we suggest that studies of nest structure may be sentinels for the early signs of rapid climate change

Dengue virus infections are an emerging global threat. Severe dengue infection is manifested as dengue hemorrhagic fever and dengue shock syndrome, both of which can be fatal complications. Factors predisposing to complicated disease and pathogenesis of severe infections are discussed. Using immunohistochemistry, immunofluorescence, flow cytometry, and ELISA techniques, we studied the cellular targets of dengue virus infection, at both the clinical (in vivo) and the laboratory (in vitro) level. Resident skin dendritic cells are targets of dengue virus infection as demonstrated in a skin biopsy from a dengue vaccine recipient. We show that factors influencing infection of monocytes/macrophages and dendritic cells are different. Immature dendritic cells were found to be the cells most permissive for dengue infection and maybe early targets for infection. Immature dendritic cells exposed to dengue virus produce TNF-alpha protein. Some of these immature dendritic cells undergo TNF-alpha mediated maturation as a consequence of exposure to the dengue virus.

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