| Author | Henriques, Priscilla Miranda | |
| Author | Almeida, Gregório Guilherme | |
| Author | Rimkute, Inga | |
| Author | Santos, Luara Isabela dos | |
| Author | Liechti, Thomas | |
| Author | Marino, Ana Paula | |
| Author | Vale, Isabela Natália Pascoal Campos do | |
| Author | Vasconcelos-Santos, Daniel Vitor | |
| Author | Martins Filho, Olindo Assis | |
| Author | Gazzinelli, Ricardo Tostes | |
| Author | Roederer, Mario | |
| Author | Sher, Alan | |
| Author | Carvalho, Andréa Teixeira de | |
| Author | Jankovic, Dragana | |
| Author | Antonelli, Lis Ribeiro do Valle | |
| Access date | 2025-05-06T17:53:48Z | |
| Available date | 2025-05-06T17:53:48Z | |
| Document date | 2025 | |
| Citation | HENRIQUES, Priscilla Miranda et al. Cytotoxic Signature and IFN-γ Production Dominate CD4+ T-Cell Response During Human Toxoplasmosis. Immunology, v. 175, n. 2, p. 151-164, 2025. | en_US |
| ISSN | 0019-2805 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/70195 | |
| Language | eng | en_US |
| Publisher | Wiley-Blackwell Publishing Ltd. | en_US |
| Rights | restricted access | en_US |
| Title | Cytotoxic Signature and IFN-γ Production Dominate CD4+ T-Cell Response During Human Toxoplasmosis. | en_US |
| Type | Article | en_US |
| DOI | 10.1111/imm.13912 | |
| Abstract | Toxoplasma gondii is a highly versatile parasite that infects most warm-blooded animals and is a major cause of retinochoroiditis and uveitis in humans. The pathophysiology of these conditions remains poorly understood. Both parasite virulence and host inflammatory response contribute to the development of ocular disease. While CD4+ T cells play a critical role in host resistance to Toxoplasma infection, their kinetics and effector functions, as well as their contribution to the clinical outcome of the infection, including ocular involvement, remain poorly understood. To address this question, we investigated the immune response during acute and convalescent toxoplasmosis and stratified patients further based on the presence or absence of ocular disease. We found that T. gondii infection leads to decreased and increased proportions of central and effector memory CD4+ T cells, respectively. Applying unsupervised analysis, distinct CD4+ T-cell subsets were determined. Among 50 clusters, 10 produced cytotoxic proteins (granzyme B and perforin) and one produced cytokines upon antigen-specific stimulation. We observed that proportions of five CD4+ T-cell clusters out of 50 were different during acute disease between T. gondii-infected patients with and without ocular lesions. Interestingly, three of the five displayed a cytotoxic signature indicating their possible involvement in ocular immunopathology. Taken together, our results reveal that during T. gondii infection, CD4+ T cells not only develop a Th1 cytokine profile, but also acquire previously unappreciated cytotoxic capacity/function. These results, while underscoring the complexity of the CD4+ T-cell response to T. gondii, suggest that specific subsets may be involved in the development of pathology and provide possible targets for therapeutic intervention. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Biologia e Imunologia de Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Biologia e Imunologia de Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Vaccine Research Center. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, Maryland, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Biologia e Imunologia de Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil. / Faculdade de Ciências Médicas de Minas Gerais. Departamento de Ciências Básicas. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Vaccine Research Center. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, Maryland, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Biologia e Imunologia de Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Biologia e Imunologia de Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Oftalmologia e Otorrinolaringologia. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisa em Biomarcadores. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Vaccine Research Center. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, Maryland, USA. | en_US |
| Affilliation | Immunobiology Section, Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, Maryland, USA | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisa em Biomarcadores. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Immunobiology Section, Laboratory of Parasitic Diseases. National Institute of Allergy and Infectious Diseases. National Institutes of Health. Bethesda, Maryland, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Biologia e Imunologia de Doenças Infecciosas e Parasitárias. Belo Horizonte, MG, Brasil. | en_US |
| Subject | CD4+ T cells | en_US |
| Subject | Cytotoxic T cells | en_US |
| Subject | Human toxoplasmosis | en_US |
| Subject | Toxoplasma gondii | en_US |
| Embargo date | 3100-12-31 | |
