Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/36200
Title: CXCR3 chemokine receptor guides Trypanosoma cruzi-specific T-cells triggered by DNA/adenovirus ASP2 vaccine to heart tissue after challenge
Authors: Ferreira, Camila Pontes
Cariste, Leonardo Moro
Moraschi, Barbara Ferri
Zanetti, Bianca Ferrarini
Han, Sang Won
Ribeiro, Daniel Araki
Machado, Alexandre Vieira
Lannes-Vieira, Joseli
Gazzinelli, Ricardo Tostes
Vasconcelos, José Ronnie Carvalho
Affilliation: Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.
Universidade Federal de São Paulo. Departamento de Biociências. Santos, SP, Brasil.
Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.
Universidade Federal de São Paulo. Departamento de Biofísica. São Paulo, SP, Brasil.
Universidade Federal de São Paulo. Departamento de Biofísica. São Paulo, SP, Brasil.
Universidade Federal de São Paulo. Departamento de Biociências. Santos, SP, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester. USA.
Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil / Universidade Federal de São Paulo. Departamento de Biociências. Santos, SP, Brasil.
Abstract: CD8+ T lymphocytes play an important role in controlling infections by intracellular pathogens. Chemokines and their receptors are crucial for the migration of CD8+ T-lymphocytes, which are the main IFNγ producers and cytotoxic effectors cells. Although the participation of chemokine ligands and receptors has been largely explored in viral infection, much less is known in infection by Trypanosoma cruzi, the causative agent of Chagas disease. After T. cruzi infection, CXCR3 chemokine receptor is highly expressed on the surface of CD8+ T-lymphocytes. Here, we hypothesized that CXCR3 is a key molecule for migration of parasite-specific CD8+ T-cells towards infected tissues, where they may play their effector activities. Using a model of induction of resistance to highly susceptible A/Sn mice using an ASP2-carrying DNA/adenovirus prime-boost strategy, we showed that CXCR3 expression was upregulated on CD8+ T-cells, which selectively migrated towards its ligands CXCL9 and CXCL10. Anti-CXCR3 administration reversed the vaccine-induced resistance to T. cruzi infection in a way associated with hampered cytotoxic activity and increased proapoptotic markers on the H2KK-restricted TEWETGQI-specific CD8+ T-cells. Furthermore, CXCR3 receptor critically guided TEWETGQI-specific effector CD8+ T-cells to the infected heart tissue that express CXCL9 and CXCL10. Overall, our study pointed CXCR3 and its ligands as key molecules to drive T. cruzi-specific effector CD8+ T-cells into the infected heart tissue. The unveiling of the process driving cell migration and colonization of infected tissues by pathogen-specific effector T-cells is a crucial requirement to the development of vaccine strategies.
Keywords: Trypanosoma cruzi
Chagas disease
Vaccine strategies
Issue Date: 2019
Publisher: Public Library of Science
Citation: FERREIRA, Camila Pontes et al. CXCR3 chemokine receptor guides Trypanosoma cruzi-specific T-cells triggered by DNA/adenovirus ASP2 vaccine to heart tissue after challenge. PLoS Neglected Tropical Diseases, v. 13, n. 7, p. 1-27, 2019.
DOI: 10.1371/journal.pntd.0007597
ISSN: 1935-2735
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos
MG - IRR - Artigos de Periódicos

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