| Author | Borges-Fernandes, Luana Oliveira | |
| Author | Moreira, Marcela de Lima | |
| Author | Pereira, Victória Hellena Silva | |
| Author | Xavier, Marcelo Antônio Pascoal | |
| Author | Ribeiro, Ágata Lopes | |
| Author | Rocha, Ismael Artur da Costa | |
| Author | Lopes, Ludmila Rosa | |
| Author | Moreira, Guilherme Telles Cristo | |
| Author | Araújo, Márcio Sobreira da Silva | |
| Author | Carvalho, Andréa Teixeira de | |
| Author | Sousa, Joaquim Pedro Brito de | |
| Author | Carvalho, Andrea Lucchesi de | |
| Author | Mourão, Maria Vitória Assumpção | |
| Author | Campos, Flávia Alves | |
| Author | Borges, Marineide | |
| Author | Carneiro, Mariângela | |
| Author | Tsuji, Moriya | |
| Author | Martins Filho, Olindo Assis | |
| Author | Reis, Jordana Grazziela Alves Coelho Dos | |
| Author | Pascoal, Vanessa Peruhype Magalhães | |
| Access date | 2024-09-19T13:20:05Z | |
| Available date | 2024-09-19T13:20:05Z | |
| Document date | 2024 | |
| Citation | BORGES-FERNANDES, Luana Oliveira et al. MR1 blockade drives differential impact on integrative signatures based on circuits of circulating immune cells and soluble mediators in visceral leishmaniasis. Frontiers in Immunology, v. 15, p. 1-14, Aug. 2024. | en_US |
| ISSN | 1664-3224 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/65950 | |
| Language | eng | en_US |
| Publisher | Frontiers Research Foundation | en_US |
| Rights | open access | en_US |
| Title | MR1 blockade drives differential impact on integrative signatures based on circuits of circulating immune cells and soluble mediators in visceral leishmaniasis | en_US |
| Type | Article | en_US |
| DOI | 10.3389/fimmu.2024.1373498 | |
| Abstract | Introduction: Visceral leishmaniasis (VL) is an important tropical and neglected disease and represents a serious global health problem. The initial interaction between the phagocytes and the parasite is crucial to determine the pathogen's capacity to initiate infection and it shapes the subsequent immune response that will develop. While type-1 T-cells induce IL-6, IL-1β, TNF-α, and IL-12 production by monocytes/macrophages to fight the infection, type-2 T-cells are associated with a regulatory phenotype (IL-10 and TGF-β) and successful infection establishment. Recently, our group demonstrated the role of an important Th1/Th17 T-cell population, the mucosal-associated invariant T (MAIT) cells, in VL. MAIT cells can respond to L. infantum by producing TNF-α and IFN-γ upon MR1-dependent activation. Objective and methods: Here, we describe the impact of the MR1-blockage on L. infantum internalization on the functional profile of circulating neutrophils and monocytes as well as the impact of the MR1-blockage on the soluble mediator signatures of in vitro whole blood cultures.
Results: Overall, our data showed that VL patients presents higher percentage of activated neutrophils than asymptomatic and non-infected controls. In addition, MR1 blockade led to lower TNF-α and TGF-β production by non-activated neutrophils from asymptomatic individuals. Moreover, TNF-α and IL-10 production by monocytes was higher in VL patients. In the analysis of soluble mediators produced in vitro, MR1-blockade induced a decrease of IFN-γ and an increase of IL-10, IL-27 and IL-33 in the cell cultures of AS group, a cytokine pattern associated with type 2 deleterious response. Discussion and conclusion: These data corroborate the hypothesis that MR1-restricted responses are associated to a protective role during Leishmania infection. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/School of Medicine. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Basic and Applied Virology Laboratory. Department of Microbiology. Institute for Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | João Paulo II Children's Hospital. Fundação Hospitalar do Estado de Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | João Paulo II Children's Hospital. Fundação Hospitalar do Estado de Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | João Paulo II Children's Hospital. Fundação Hospitalar do Estado de Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | João Paulo II Children's Hospital. Fundação Hospitalar do Estado de Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Parasitology Department. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | Aaron Diamond AIDS Research Center. Columbia University Vagelos College of Physicians and Surgeons. New York, NY, United States/Division of Infectious Disease. Department of Medicine. Columbia University Vagelos College of Physicians and Surgeons. New York, NY, United States. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil/Basic and Applied Virology Laboratory. Department of Microbiology. Institute for Biological Sciences. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
| Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
| Subject | Visceral leishmaniasis (VL) | en_US |
| Subject | MR1 blockade | en_US |
| Subject | Cytokines | en_US |
| Subject | Integrative circuits | en_US |
| Subject | Internalization | en_US |
| Subject | Nitric oxide | en_US |
| Subject | Phagocytes | en_US |
| Subject | Soluble mediators | en_US |
