Dendritic cell-based vaccination strategies: induction of protective immunity against leishmaniasis

The clinical symptoms caused by infections with Leishmania parasites range from self-healing cutaneous to uncontrolled visceral disease and depend not only on the parasite species but also on the type of the host's immune response. Infection of genetically susceptible mice with Leishmania major results in the development of disease-promoting T helper cells of type 2 (Th2). On the other hand, healing of lesions is dependent on the induction of Th1 cells producing interferon-gamma (IFN-gamma). The presence of interleukin 12 (IL-12) is known to be crucial for the differentiation of Th1 cells. Whereas IL-12 release and the T cell stimulatory functions of macrophages are down-regulated by L. major infection, dendritic cells (DC) exposed to L. major readily produce IL-12 and are highly potent antigen-presenting cells. Moreover, DC pulsed ex vivo with L. major antigen induce protection in otherwise susceptible mice against subsequent challenges with the parasites. The protection is long-lasting and correlates with a shift of the cytokine expression pattern towards a Th1 response. Thus, DC serve as immunomodulators in vivo and can be used as an effective adjuvant for vaccination against experimental leishmaniasis. Studies on the ability of DC to induce protective immunity to leishmaniasis may have important implications for the development of novel strategies for prophylactic and therapeutic immunizations against microbial pathogens.