Abstract
BackgroundDendritic cells localize throughout the body, where they can sense and capture invading pathogens to induce protective immunity. Hence, harnessing the biology of tissue-resident dendritic cells is fundamental for the rational design of vaccines against pathogens.MethodsHerein, we characterized the transcriptomes of four antigen-presenting cell subsets from the human vagina (Langerhans cells, CD14- and CD14+ dendritic cells, macrophages) by microarray, at both the transcript and network level, and compared them to those of three skin dendritic cell subsets and blood myeloid dendritic cells.ResultsWe found that genomic fingerprints of antigen-presenting cells are significantly influenced by the tissue of origin as well as by individual subsets. Nonetheless, CD14+ populations from both vagina and skin are geared towards innate immunity and pro-inflammatory responses, whereas CD14- populations, particularly skin and vaginal Langerhans cells, and vaginal CD14- dendritic cells, display both Th2-inducing and regulatory phenotypes. We also identified new phenotypic and functional biomarkers of vaginal antigen-presenting cell subsets.ConclusionsWe provide a transcriptional database of 87 microarray samples spanning eight antigen-presenting cell populations in the human vagina, skin and blood. Altogether, these data provide molecular information that will further help characterize human tissue antigen-presenting cell lineages and their functions. Data from this study can guide the design of mucosal vaccines against sexually transmitted pathogens.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-014-0098-y) contains supplementary material, which is available to authorized users.
Highlights
Dendritic cells localize throughout the body, where they can sense and capture invading pathogens to induce protective immunity
We recently reported the presence of four major subsets of antigen-presenting cell (APC) in the human vaginal mucosa, including Langerhans cells (LCs) in the epithelium, and CD14- dendritic cell (DC), CD14+ DCs and macrophages (Møs) in the lamina propria (LP) [5,6]
Unsupervised analysis enabled the measurement of the transcriptional separation between APC populations in an unbiased fashion. vLCs were similar to vCD14- DCs, while vCD14+ DCs were similar to vMøs, suggesting that CD14 expression can be used to differentiate between two main APC groups with distinct fingerprints
Summary
Dendritic cells localize throughout the body, where they can sense and capture invading pathogens to induce protective immunity. Harnessing the biology of tissue-resident dendritic cells is fundamental for the rational design of vaccines against pathogens. DCs disseminate throughout the body, sensing invading pathogens in various tissues, including the skin [2,3,4] and mucosa [5,6,7]. Defining the biology of tissue-resident DCs is fundamental for the understanding of tissue-specific immune microenvironments and for the rational design of Sexually transmitted microbial pathogens, including viruses and bacteria [8,9], are a major public health burden worldwide. The human vaginal mucosa is the main entry site of these pathogens and has long been attractive as a potential site for mounting protective mucosal immunity.
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