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.

Figure 1. Human vaginal mucosa harbors four major populations of antigen-presenting cells that display shared and distinct functions at inducing T cell responses

Four subsets of myeloid-derived APCs are found in human vaginal mucosa: LCs in the epithelium and CD14⁻ LP-DCs, CD14⁺ LP-DCs and macrophages (MØ) in the submucosa. Each population displays shared and distinct phenotype and functions at inducing naive T cells responses.

Figure 2. DC receptors expressed in human vagina mucosa

Immunohistochemistry staining of frozen tissue sections with anti-DC-SIGN (clone 15C4, in house), anti-LOX-1 (clone 15C4, in house), anti-Langerin (clone 15E2, in house), anti-DEC205 (clone MG38, eBioscience), anti-DCIR (clone 9E8, in house) antibodies or isotype controls. Digital images were taken using an Olympus BX60 with a UPlanFl 10×/0.30 Ph1 objective, a Nikon Digital Camera DXM 1200C camera and Nikon Elements software (Nikon). (×10, bar is 100µm)