Vaccines and the regulatory arm of the immune system. An overview from the Trypanosoma cruzi infection model.

The knowledge that the immune system is composed of a regulatory/suppressor arm added a new point of view to better understand the nature of several pathologies including cancer, transplants, infections and autoimmune diseases. The striking discoveries concerning molecules and cells involved in this kind of regulation were followed by the elucidation of equally notable mechanisms used by several pathogens to manipulate the host immune system. Vaccines against pathogens are an invaluable tool developed to help the immune system cope with a potential infection or prevent disease pathology. Nowadays, there is accumulated evidence indicating that the powerful stimulation capacity of vaccines influences not only the effector arm of the immune system but also cells with regulatory/suppressor capacity, such as myeloid derived suppressor cells (MDSCs) and Foxp3+ regulatory T cells (Tregs). Trypanosoma cruzi (T. cruzi) is a protozoan parasite with a complex life cycle that has evolved several strategies to influence the regulatory immune response. Although diverse vaccine formulations have been able to stimulate the effector response, achieving non-sterilizing protection against T. cruzi, the influence of the vaccine candidates on the regulatory machinery has scarcely been assessed. This fact may not only reveal important information concerning how vaccines may influence cells with regulatory/suppressor capacity but also open the possibility to analyze whether vaccines are able to disrupt the mechanisms used by some pathogens to manipulate the host regulatory circuits. The aim of this review is to summarize and discuss available data related to the role of cellular components, like MDSCs and Foxp3+ Tregs, during T. cruzi infection, and the potential utility of those populations as additional targets for the rational design of vaccines.