Transcriptional fingerprints of antigen-presenting cell subsets in the human vaginal mucosa and skin reflect tissue-specific immune microenvironments.

BACKGROUND: Dendritic 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. METHODS: Herein, 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. RESULTS: We 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. CONCLUSIONS: We 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.

Dexmedetomidine infusion for analgesia up to 48 hours after lung surgery performed by lateral thoracotomy.

Patients undergoing a lateral thoracotomy for pulmonary resection have moderate to severe pain postoperatively that is often treated with opioids. Opioid side effects such as respiratory depression can be devastating in patients with already compromised respiratory function. This prospective double-blinded clinical trial examined the analgesic effects and safety of a dexmedetomidine infusion for postthoracotomy patients when administered on a telemetry nursing floor, 24 to 48 hours after surgery, to determine if the drug's known early opioid-sparing properties were maintained. Thirty-eight thoracotomy patients were administered dexmedetomidine intraoperatively and overnight postoperatively and then randomized to receive placebo or dexmedetomidine titrated from 0.1 to 0.5 µg·kg·h(-1) the day following surgery for up to 24 hours on a telemetry floor. Opioids via a patient-controlled analgesia pump were available for both groups, and vital signs including transcutaneous carbon dioxide, pulse oximetry, respiratory rate, and pain and sedation scores were monitored. The dexmedetomidine group used 41% less opioids but achieved pain scores equal to those of the placebo group. The mean heart rate and systolic blood pressure were lower in the dexmedetomidine group but sedation scores were better. The mean respiratory rate and oxygen saturation were similar in the two groups. Mild hypercarbia occurred in both groups, but periods of significant respiratory depression were noted only in the placebo group. Significant hypotension was noted in one patient in the dexmedetomidine group in conjunction with concomitant administration of a beta-blocker agent. The placebo group reported a higher number of opioid-related adverse events. In conclusion, the known opioid-sparing properties of dexmedetomidine in the immediate postoperative period are maintained over 48 hours.

Dendritic cells and vaccine design for sexually-transmitted diseases.

Dendritic cells (DCs) are major antigen presenting cells (APCs) that can initiate and control host immune responses toward either immunity or tolerance. These features of DCs, as immune orchestrators, are well characterized by their tissue localizations as well as by their subset-dependent functional specialties and plasticity. Thus, the level of protective immunity to invading microbial pathogens can be dependent on the subsets of DCs taking up microbial antigens and their functional plasticity in response to microbial products, host cellular components and the cytokine milieu in the microenvironment. Vaccines are the most efficient and cost-effective preventive medicine against infectious diseases. However, major challenges still remain for the diseases caused by sexually-transmitted pathogens, including HIV, HPV, HSV and Chlamydia. We surmise that the establishment of protective immunity in the female genital mucosa, the major entry and transfer site of these pathogens, will bring significant benefit for the protection against sexually-transmitted diseases. Recent progresses made in DC biology suggest that vaccines designed to target proper DC subsets may permit us to establish protective immunity in the female genital mucosa against sexually-transmitted pathogens.