Epithelial dendritic cells vs. Langerhans cells: Implications for mucosal vaccines.

Next-generation vaccines may be delivered via the skin and mucosa. The stratified squamous epithelium (SSE) represents the outermost layer of the skin (epidermis) and type II mucosa (epithelium). Langerhans cells (LCs) have been considered the sole antigen-presenting cells (APCs) to inhabit the SSE; however, it is now clear that dendritic cells (DCs) are also present. Importantly, there are functional differences in how LCs and DCs take up and process pathogens as well as their ability to activate and polarize T cells, though whether DCs participate in neuroimmune interactions like LCs is yet to be elucidated. A correct definition and functional characterization of APCs in the skin and anogenital tissues are of utmost importance for the design of better vaccines and blocking pathogen transmission. Here, we provide a historical perspective on the evolution of our understanding of the APCs that inhabit the SSE, including a detailed review of the most recent literature.

Manipulation of Mononuclear Phagocytes by HIV: Implications for Early Transmission Events.

Mononuclear phagocytes are antigen presenting cells that play a key role in linking the innate and adaptive immune systems. In tissue, these consist of Langerhans cells, dendritic cells and macrophages, all of which express the key HIV entry receptors CD4 and CCR5 making them directly infectible with HIV. Mononuclear phagocytes are the first cells of the immune system to interact with invading pathogens such as HIV. Each cell type expresses a specific repertoire of pathogen binding receptors which triggers pathogen uptake and the release of innate immune cytokines. Langerhans cells and dendritic cells migrate to lymph nodes and present antigens to CD4 T cells, whereas macrophages remain tissue resident. Here we review how HIV-1 manipulates these cells by blocking their ability to produce innate immune cytokines and taking advantage of their antigen presenting cell function in order to gain transport to its primary target cells, CD4 T cells.

Evidence of the circulation of pandemic influenza (H1N1) 2009 with D222D/G/N/S hemagglutinin polymorphisms during the first wave of the 2009 influenza pandemic.

BACKGROUND: The hemagglutinin HA1 D222G substitution may be associated with adverse outcomes in pandemic influenza A (H1N1) 2009 infections by enhancing the binding capacity of α2-3 sialyl receptors to pandemic influenza (H1N1) 2009 viruses. OBJECTIVES: To investigate the emergence of the D222G mutation and other polymorphisms at this position during the first southern hemisphere pandemic wave in 2009. STUDY DESIGN: A total of 127 samples that were nucleic acid test positive for pandemic influenza (H1N1) 2009 virus were subjected to a sequence-based genotypic assessment of viral populations. Specimens showing polymorphisms at position 222 were further cloned to characterise the viral quasispecies. RESULTS: A high proportion of intensive care unit (ICU) admissions (20%) and outpatients with mild symptoms (11.3%) carried polymorphisms of D/G/N/S at position 222 in hemagglutinin. Viral quasispecies derived from the upper and lower respiratory tract (URT and LRT) in ICU patients showed comparable levels of 222G populations. CONCLUSION: The detection of 222G quasispecies present in the URT in both ICU and outpatient groups suggest ready transmission of these variants, and its frequent detection (and clusters) in outpatients imply local community transmission.