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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Parasite Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1373498
This article is part of the Research Topic Leishmaniasis and Immunity: Challenges, Advances and Future Perspective View all 8 articles

MR1 blockade drives differential impact on integrative signatures based on circuits of circulating immune cells and soluble mediators in visceral leishmaniasis

Provisionally accepted
Luana Borges-Fernandes Luana Borges-Fernandes 1Marcela De Lima Moreira Marcela De Lima Moreira 1Victoria Pereira Victoria Pereira 1Marcelo Antônio Pascoal-Xavier Marcelo Antônio Pascoal-Xavier 1Ágata Lopes Ribeiro Ágata Lopes Ribeiro 1,2Ismael Artur D. Costa-Rocha Ismael Artur D. Costa-Rocha 1Ludmila R. Lopes Ludmila R. Lopes 1Guilherme T. Moreira Guilherme T. Moreira 1Marcio Araujo Marcio Araujo 1Andréa Teixeira-Carvalho Andréa Teixeira-Carvalho 1Andrea L. de Carvalho Andrea L. de Carvalho 3Maria Vitória A. Mourão Maria Vitória A. Mourão 3Flávia A. Campos Flávia A. Campos 3Marineide Borges Marineide Borges 3Mariangela Carneiro Mariangela Carneiro 4Moriya Tsuji Moriya Tsuji 5Olindo A. Martins-Filho Olindo A. Martins-Filho 1Jordana Grazziela A. Coelho-dos-Reis Jordana Grazziela A. Coelho-dos-Reis 1,2Vanessa Peruhype-Magalhães Vanessa Peruhype-Magalhães 1*
  • 1 René Rachou Institute, Oswaldo Cruz Foundation (Fiocruz), Belo Horizonte, Minas Gerais, Brazil
  • 2 Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
  • 3 João Paulo II Children’s Hospital - Fundação Hospitalar do Estado de Minas Gerais, Belo Horizonte, Brazil
  • 4 Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Mato Grosso, Brazil
  • 5 Aaron Diamond AIDS Research Center, New York, New York, United States

The final, formatted version of the article will be published soon.

    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-1, TNF-, 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-) 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- and IFN- 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- and TGF- production by non-activated neutrophils from asymptomatic individuals. Moreover, TNF- 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- 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.

    Keywords: MR1 blockade, L. infantum, Phagocytes, Soluble mediators, Integrative circuits, Cytokines, Nitric Oxide, internalization

    Received: 19 Jan 2024; Accepted: 15 Jul 2024.

    Copyright: © 2024 Borges-Fernandes, De Lima Moreira, Pereira, Pascoal-Xavier, Lopes Ribeiro, Costa-Rocha, Lopes, Moreira, Araujo, Teixeira-Carvalho, de Carvalho, Mourão, Campos, Borges, Carneiro, Tsuji, Martins-Filho, Coelho-dos-Reis and Peruhype-Magalhães. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Vanessa Peruhype-Magalhães, René Rachou Institute, Oswaldo Cruz Foundation (Fiocruz), Belo Horizonte, 1715, Minas Gerais, Brazil

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