Abstract
Prophylactic and/or therapeutic vaccines have an important potential to control Trypanosoma cruzi (T. cruzi)infection. The involvement of regulatory/suppressor immune cells after an immunization treatment and T. cruzi infection has never been addressed. Here we show that a new trans-sialidase-based immunogen (TSf) was able to confer protection, correlating not only with beneficial changes in effector immune parameters, but also influencing populations of cells related to immune control.Regarding the effector response, mice immunized with TSf showed a TS-specific antibody response, significant delayed-type hypersensitivity (DTH) reactivity and increased production of IFN-γ by CD8+ splenocytes. After a challenge with T. cruzi, TSf-immunized mice showed 90% survival and low parasitemia as compared with 40% survival and high parasitemia in PBS-immunized mice.In relation to the regulatory/suppressor arm of the immune system, after T. cruzi infection TSf-immunized mice showed an increase in spleen CD4+ Foxp3+ regulatory T cells (Treg) as compared to PBS-inoculated and infected mice. Moreover, although T. cruzi infection elicited a notable increase in myeloid derived suppressor cells (MDSC) in the spleen of PBS-inoculated mice, TSf-immunized mice showed a significantly lower increase of MDSC.Results presented herein highlight the need of studying the immune response as a whole when a vaccine candidate is rationally tested.
Highlights
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi (T. cruzi)
It has been previously shown that the TS sequence indexed in the GenBank AJ276679 codifies for a TS protein that has protective capacity against T. cruzi infection [15]
Our results strongly suggest that TS fragment obtained (TSf)-ISPA formulation mainly influenced the G-myeloid derived suppressor cells (MDSC) population (CD11b+Ly6G+Ly6C+) after T. cruzi infection, without severely affecting the monocytic MDSC (M-MDSC) population (CD11b+Ly6G-Ly6C+)
Summary
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi (T. cruzi). Chagas disease can be treated with benznidazole or nifurtimox during the acute phase of the disease, the efficiency of both drugs is still unclear in chronic patients, who may suffer some adverse reactions, occurring in up to 40% of treated patients [3], [4]. A recent multicenter trial has shown that chemotherapeutic treatment dampens parasite load but does not decrease morbility nor mortality associated with the Chagas disease cardiomyopathy [5]. Prophylactic and therapeutic vaccines would be suitable alternatives for preventing and/ or treating Chagas disease. Several studies have focused on characterization of parasite antigens which may be used as vaccine candidates. Some recombinant or purified antigens have shown promising results in mouse models, such as paraflagellar rod proteins, trypomastigote excretory-secretory antigens, glycoprotein 82, trypomastigote surface antigen 1, Tc52, cruzipain and trans-sialidase (TS) [6], [7], [8], [9], [10], [11], [12]
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