Fragments of antigen-loaded dendritic cells (DC) and DC-derived exosomes induce protective immunity against Leishmania major.

Upon loading with parasite antigen and adoptive transfer, dendritic cells (DC) are able to confer protection against the protozoan parasite Leishmania major. In the present study, we investigated whether viable DC are required for inducing protection. We provide evidence that L. major antigen-loaded DC that had been fixed with paraformaldehyde or exposed to UV irradiation, and even disrupted cells, are able to serve as an effective vaccine. Furthermore, we demonstrate the potential of DC-derived exosomes to mediate protective immunity against cutaneous leishmaniasis. The route of antigen presentation to recipient T cells involves uptake of intravenously injected DC fragments into late endosomal compartments of splenic DC in the recipient. In vitro studies showed that DC fragments induce T-cell proliferation and interleukin 12 secretion by splenocytes. Together, these findings suggest that the development of a cell-free vaccine for immunoprophylaxis against leishmaniasis and other infectious diseases is feasible.

Mechanisms of dendritic cell-based vaccination against infection.

Due to their unique capacity to initiate and regulate adaptive immune responses, dendritic cells (DC) represent the most potent antigen-presenting cells of the immune system. Immature DC reside in peripheral tissues, where they sample and process antigens and efficiently sense a large variety of signals from the surrounding environment. Toll-like receptors (TLR) expressed by DC play a critical role in the detection of invading pathogens as well as in triggering the subsequent immune responses. The differential expression of TLR by different DC subsets may correlate with the induction of different patterns of adaptive immune responses. The rapidly expanding and fundamental knowledge of DC biology furthers promising perspectives for the development of vaccination strategies in different fields. For example, the immunotherapeutic potential of antigen-pulsed DC for the treatment of cancer has been confirmed in a number of experimental tumour models. Furthermore, DC have been shown to serve as natural adjuvants in different models of infectious diseases, mediating protection against various types of pathogens. Using murine leishmaniasis as an example, we have demonstrated that DC, once properly conditioned ex vivo, mediate complete and durable protection against infection. Critical parameters determining the efficiency of DC-based vaccination against microbial pathogens include the origin of DC, the choice of antigen to be used for DC loading, the route of immunization and the state of DC maturation and activation. In the present review, we discuss the necessity to define the mechanisms responsible for the immunostimulatory capacity of DC in vivo, in order to exploit their full potential as vaccination tools.