Abstract
CD8 T cells are regarded as pivotal players in both immunoprotection and immunopathology following Trypanosoma cruzi infection. Previously, we demonstrated the expansion of CD8+ T lymphocytes in the spleen of T. cruzi-infected mice under treatment with benznidazole (N-benzyl-2-nitroimidazole acetamide; Bz), a drug available for clinical therapy. This finding underlies the concept that the beneficial effects of Bz on controlling acute T. cruzi infection are related to a synergistic process between intrinsic trypanocidal effect and indirect triggering of the active immune response. In the present study, we particularly investigated the effect of Bz treatment on the CD8+ T cell subset following T. cruzi infection. Herein we demonstrated that, during acute T. cruzi infection, Bz treatment reduces and abbreviates the parasitemia, but maintains elevated expansion of CD8+ T cells. Within this subset, a remarkable group of CD8low cells was found in both Bz-treated and non-treated infected mice. In Bz-treated mice, early pathogen control paralleled the lower frequency of recently activated CD8low cells, as ascertained by CD69 expression. However, the CD8low subset sustains significant levels of CD44highCD62Llow and CD62LlowT-bethigh effector memory T cells, in both Bz-treated and non-treated infected mice. These CD8low cells also comprise the main group of spontaneous interferon (IFN)-γ-producing CD8+ T cells. Interestingly, following in vitro anti-CD3/CD28 stimulation, CD8+ T cells from Bz-treated T. cruzi-infected mice exhibited higher frequency of IFN-γ+ cells, which bear mostly a CD8low phenotype. Altogether, our results point to the marked presence of CD8low T cells that arise during acute T. cruzi infection, with Bz treatment promoting their significant expansion along with a potential effector program for high IFN-γ production.
Highlights
IntroductionTrypanosoma cruzi is the etiologic agent of Chagas disease, a neglected illness considered a global health problem which affects around 6–8 million people worldwide [1,2]
Chagas disease is a neglected illness caused by the protozoan Trypanosoma cruzi, which affects 6 to 7 million people worldwide
We previously suggested that CD8+ T cells, highly expanded after Bz treatment of acute T. cruzi-infected mice, might play a particular role in parasite control
Summary
Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected illness considered a global health problem which affects around 6–8 million people worldwide [1,2]. Countries with vectorial transmission of Chagas disease are reporting outbreaks of oral infection by ingestion of contaminated food [3,4]. The immune response reduces the parasite burden, the infection is not eliminated [8]. Parasite persistence [9] is likely to contribute to the effects of long-term T. cruzi infection, which might induce gradual progression towards a severe symptomatology observed in a high proportion of infected individuals [10]. CD8+ T cells have been regarded as critical players for both immunoprotection and immunopathological disturbances observed in experimental and clinical studies [11,12,13,14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
