Dendritic cells and vaccine design for sexually-transmitted diseases

Abstract

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.

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

“…LOX-1 was also expressed at low levels on vCD14 - DCs (Figure 7 b,c). Transcriptional levels of CD207 were low in all vaginal APC subsets, despite detectable protein levels on the surface of vLCs (Figure 1 b), as previously reported [ 5 , 6 ]. DC-ASGPR was detected in a few vLCs and approximately 50% (49.06 ± 25) of vCD14 - DCs (Figure 7 b, c).…”

“…Finally, it is important to note that the individual APC populations we describe in this manuscript may contain additional levels of heterogeneity. For example, we have previously shown that both CD14 - and CD14 + LP-DCs could be further separated into two subpopulations based on CD1a expression [ 5 , 6 ]. Further studies, such as single-cell RNA sequencing of populations of interest, are warranted to further characterize the heterogeneity of these populations.…”

“…We recently reported the presence of four major subsets of APCs in the human vaginal mucosa, including Langerhans cells (LCs) in the epithelium, and CD14 - DCs, CD14 + DCs and macrophages (Møs) in the lamina propria (LP) [ 5 , 6 ]. These mucosal APC subsets display common and unique functions in directing T-cell responses in vitro [ 5 , 6 ], as do subsets of DCs isolated from human skin [ 2 - 4 ]. Importantly, DCs can display functional specialization and plasticity in response to external and internal stimuli [ 13 , 14 ], which can determine the outcome of host immune responses.…”

“…These differences may also influence the type of immunity established in different human anatomical sites. As such, vaccines delivered to skin DCs can elicit systemic immunity but are not sufficient to mount mucosal immunity [ 6 , 10 , 17 ].…”

Anti-apoptotic function of herpes simplex virus -2 latency-associated transcript RL1 sequence and screening of its encoded microRNAs

“…Identification of miRNAs encoded by DNA viruses indicate that viruses have evolved to build on RNA silencing to regulate host and viral genes. miRNAs encoded by viruses can affect the viral life cycle and host physiology . Herpes simplex virus (HSV)‐1 and HSV‐2 are two members of a group of pathogenic human viruses belonging to the alphaherpesvirus subfamily .…”