Science on the Screen is the Biology Department new Online Seminars Cycle in which invited scientists will talk about science and their research in about 30 minutes.
Alexandra Correia - I3S (U.Porto)
24 May | 12:00 | videoconf link
Resumo/Abstract
Infection by parasitic protozoa of the phylum Apicomplexa causes substantial morbidity and mortality to humans and livestock. Apicomplexan parasites include Plasmodium spp., the agents of malaria; Toxoplasma gondii, an important opportunistic pathogen in immunocompromised individuals, and Neospora caninum, a leading cause of abortion in cattle. Vaccination is considered the most cost-effective approach to manage apicomplexan diseases, however, no effective commercial vaccines for human toxoplasmosis and cattle neosporosis are available to date. Parasites are major modulators of the immune system, so that immunity is often incomplete, supporting transmission. Protective immunity against apicomplexan parasites is generally T cell-dependent and elicited along the IL-12/IFN-gamma effector axis. Vaccine adjuvants and new immunization strategies that can promote potent protective immunity is thus urgent. We have developed an experimental mucosal vaccine for neosporosis, using N. caninum membrane antigens plus CpG adjuvant, that induced the generation of IFN-gamma-producing memory T cells and conferred long-term protection to mice challenged with this parasite. Our vaccination strategy was also attempted against T. gondii infection, reducing parasitic burden in several organs. Protection against neosporosis was mainly mediated by IFN-gamma-dependent induction of parasite microbicidal mechanisms in macrophages, since immunized mice with macrophages insensitive to IFN-gamma, failed to control N. infection. Interestingly, IFN-gamma-signaling in endothelial cells also contributes to protection. Conditional KO mice in which endothelial cells do not respond to IFN-gamma are more susceptible to neosporosis than the WT littermates, and protection conferred by immunization is abolished in those mice. The obtained results indicate that by using intranasal administration and a strong Th1-directing adjuvant, we can boost effective IFN-gamma-mediated protection, both at mucosal and systemic levels, through macrophage and endothelial cell activation.