Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/35518
Title: Thymic Microenvironment Is Modified by Malnutrition and Leishmania infantum Infection
Authors: Losada-Barragán, Monica
Umaña-Pérez, Adriana
Durães, Jonathan
Cuervo-Escobar, Sergio
Rodríguez-Vega, Andrés
Ribeiro-Gomes, Flávia L.
Berbert, Luiz R.
Morgado, Fernanda
Porrozzi, Renato
Cruz, Daniella Arêas Mendes da
Aquino, Priscila
Carvalho, Paulo C.
Savino, Wilson
Sánchez-Gómez, Myriam
Padrón, Gabriel
Cuervo, Patricia
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmanioses. Rio de Janeiro, RJ, Brasil / Universidad Antonio Nariño. Departamento de Biologia. Grupo de Investigación en Biología Celular y Funcional e Ingeniería de Biomoléculas. Bogotá, Colombia.
Universidad Nacional de Colombia. Departamento de Química. Grupo de Investigación en Hormonas. Bogotá, Colombia.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmanioses. Rio de Janeiro, RJ, Brasil.
Universidad de Ciencias Aplicadas y Ambientales. Facultad de Ciencias. Bogotá, Colombia;
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmanioses. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmanioses. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmanioses. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil.
Fundação Oswaldo Cruz. Grupo de Espectrometria de Massa Computacional e Proteômica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisas sobre o Timo. Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil.
Universidad Nacional de Colombia. Departamento de Química. Grupo de Investigación en Hormonas. Bogotá, Colombia.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmanioses. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmanioses. Rio de Janeiro, RJ, Brasil.
Abstract: Detrimental effects of malnutrition on immune responses to pathogens have long been recognized and it is considered a main risk factor for various infectious diseases, including visceral leishmaniasis (VL). Thymus is a target of both malnutrition and infection, but its role in the immune response to Leishmania infantum in malnourished individuals is barely studied. Because we previously observed thymic atrophy and significant reduction in cellularity and chemokine levels in malnourished mice infected with L. infantum, we postulated that the thymic microenvironment is severely compromised in those animals. To test this, we analyzed the microarchitecture of the organ and measured the protein abundance in its interstitial space in malnourished BALB/c mice infected or not with L. infantum. Malnourished-infected animals exhibited a significant reduction of the thymic cortex:medulla ratio and altered abundance of proteins secreted in the thymic interstitial fluid. Eighty-one percent of identified proteins are secreted by exosomes and malnourished-infected mice showed significant decrease in exosomal proteins, suggesting that exosomal carrier system, and therefore intrathymic communication, is dysregulated in those animals. Malnourished-infected mice also exhibited a significant increase in the abundance of proteins involved in lipid metabolism and tricarboxylic acid cycle, suggestive of a non-proliferative microenvironment. Accordingly, flow cytometry analysis revealed decreased proliferation of single positive and double positive T cells in those animals. Together, the reduced cortical area, decreased proliferation, and altered protein abundance suggest a dysfunctional thymic microenvironment where T cell migration, proliferation, and maturation are compromised, contributing for the thymic atrophy observed in malnourished animals. All these alterations could affect the control of the local and systemic infection, resulting in an impaired response to L. infantum infection.
Keywords: Thymus
Thymic microenvironment
Protein malnutrition
Leishmania infantum
Visceral leishmaniasis
Interstitial fluid
Proteomics
Fatty acid oxidation
keywords: Leishmania infantum
Timo
Microambiente tímico
Desnutrição protéica
Fluido intersticial
Leishmaniose visceral
Proteômica
Oxidação de ácidos graxos
Issue Date: 2019
Publisher: Frontiers Media
Citation: LOSADA-BARRAGÁN, Monica et al. Thymic Microenvironment Is Modified by Malnutrition and Leishmania infantum Infection. Frontiers in Cellular and Infection Microbiology, v. 9, p.1-19, July 2019.
DOI: 10.3389/fcimb.2019.00252
ISSN: 2235-2988
Copyright: open access
Appears in Collections:AM - ILMD - Artigos de Periódicos
IOC - Artigos de Periódicos

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