Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis

The mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the es...

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Main Authors: José Alberto Choreño-Parra, Luis Armando Jiménez-Álvarez, Ellis Daniela Maldonado-Díaz, Graciela Cárdenas, Luis Alejandro Fernández-Lopez, José Luis Soto-Hernandez, Marcela Muñoz-Torrico, Gustavo Ramírez-Martínez, Alfredo Cruz-Lagunas, Armando Vega-López, María Lilia Domínguez-López, Carlos Sánchez-Garibay, Parménides Guadarrama-Ortíz, Silvia Giono, Luis Antonio Jiménez-Zamudio, Shabaana A. Khader, Ethel A. García-Latorre, Citlaltepetl Salinas-Lara, Joaquín Zúñiga
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/5517856
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author José Alberto Choreño-Parra
Luis Armando Jiménez-Álvarez
Ellis Daniela Maldonado-Díaz
Graciela Cárdenas
Luis Alejandro Fernández-Lopez
José Luis Soto-Hernandez
Marcela Muñoz-Torrico
Gustavo Ramírez-Martínez
Alfredo Cruz-Lagunas
Armando Vega-López
María Lilia Domínguez-López
Carlos Sánchez-Garibay
Parménides Guadarrama-Ortíz
Silvia Giono
Luis Antonio Jiménez-Zamudio
Shabaana A. Khader
Ethel A. García-Latorre
Citlaltepetl Salinas-Lara
Joaquín Zúñiga
author_facet José Alberto Choreño-Parra
Luis Armando Jiménez-Álvarez
Ellis Daniela Maldonado-Díaz
Graciela Cárdenas
Luis Alejandro Fernández-Lopez
José Luis Soto-Hernandez
Marcela Muñoz-Torrico
Gustavo Ramírez-Martínez
Alfredo Cruz-Lagunas
Armando Vega-López
María Lilia Domínguez-López
Carlos Sánchez-Garibay
Parménides Guadarrama-Ortíz
Silvia Giono
Luis Antonio Jiménez-Zamudio
Shabaana A. Khader
Ethel A. García-Latorre
Citlaltepetl Salinas-Lara
Joaquín Zúñiga
author_sort José Alberto Choreño-Parra
collection DOAJ
description The mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the establishment of adaptive immunity. Hence, several innate immune mechanisms may participate in the containment of Mtb infection and prevent extrapulmonary disease manifestations. Natural killer (NK) cells participate in defensive processes that distinguish latent TB infection (LTBI) from active pulmonary TB (PTB). However, their role in TBM is unknown. Here, we performed a cross-sectional analysis of circulating NK cellCID="C008" value="s" phenotype in a prospective cohort of TBM patients (n=10) using flow cytometry. Also, we addressed the responses of memory-like NK cell subpopulations to the contact with Mtb antigens in vitro. Finally, we determined plasma levels of soluble NKG2D receptor ligands in our cohort of TBM patients by enzyme-linked immunosorbent assay (ELISA). Our comparative groups consisted of individuals with LTBI (n=11) and PTB (n=27) patients. We found that NK cells from TBM patients showed lower absolute frequencies, higher CD69 expression, and poor expansion of the CD45RO+ memory-like subpopulation upon Mtb exposure in vitro compared to LTBI individuals. In addition, a reduction in the frequency of CD56brightCD16- NK cells characterized TBM patients but not LTBI or PTB subjects. Our study expands on earlier reports about the role of NK cells in TBM showing a reduced frequency of cytokine-producing cells compared to LTBI and PTB.
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spelling doaj-art-d3ea20e016da4096875013e7b87ae3cc2025-02-03T06:05:36ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/55178565517856Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal TuberculosisJosé Alberto Choreño-Parra0Luis Armando Jiménez-Álvarez1Ellis Daniela Maldonado-Díaz2Graciela Cárdenas3Luis Alejandro Fernández-Lopez4José Luis Soto-Hernandez5Marcela Muñoz-Torrico6Gustavo Ramírez-Martínez7Alfredo Cruz-Lagunas8Armando Vega-López9María Lilia Domínguez-López10Carlos Sánchez-Garibay11Parménides Guadarrama-Ortíz12Silvia Giono13Luis Antonio Jiménez-Zamudio14Shabaana A. Khader15Ethel A. García-Latorre16Citlaltepetl Salinas-Lara17Joaquín Zúñiga18Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Inmunoquímica I, Mexico City, MexicoInstituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Inmunoquímica I, Mexico City, MexicoNeuroinfectology Department, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, MexicoNeuroinfectology Department, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, MexicoInstituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Inmunoquímica I, Mexico City, MexicoNeuroinfectology Department, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, MexicoTuberculosis Clinic, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoLaboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoLaboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoInstituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Toxicología Ambiental, Mexico City, MexicoInstituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Inmunoquímica I, Mexico City, MexicoDepartment of Neuropathology, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, MexicoCentro Especializado en Neurocirugía y Neurociencias México (CENNM), Mexico City, MexicoInstituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Departamento de Microbiología, Mexico City, MexicoInstituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Inmunoquímica I, Mexico City, MexicoDepartment of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO, USAInstituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Inmunoquímica I, Mexico City, MexicoDepartment of Neuropathology, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, Mexico City, MexicoLaboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Mexico City, MexicoThe mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the establishment of adaptive immunity. Hence, several innate immune mechanisms may participate in the containment of Mtb infection and prevent extrapulmonary disease manifestations. Natural killer (NK) cells participate in defensive processes that distinguish latent TB infection (LTBI) from active pulmonary TB (PTB). However, their role in TBM is unknown. Here, we performed a cross-sectional analysis of circulating NK cellCID="C008" value="s" phenotype in a prospective cohort of TBM patients (n=10) using flow cytometry. Also, we addressed the responses of memory-like NK cell subpopulations to the contact with Mtb antigens in vitro. Finally, we determined plasma levels of soluble NKG2D receptor ligands in our cohort of TBM patients by enzyme-linked immunosorbent assay (ELISA). Our comparative groups consisted of individuals with LTBI (n=11) and PTB (n=27) patients. We found that NK cells from TBM patients showed lower absolute frequencies, higher CD69 expression, and poor expansion of the CD45RO+ memory-like subpopulation upon Mtb exposure in vitro compared to LTBI individuals. In addition, a reduction in the frequency of CD56brightCD16- NK cells characterized TBM patients but not LTBI or PTB subjects. Our study expands on earlier reports about the role of NK cells in TBM showing a reduced frequency of cytokine-producing cells compared to LTBI and PTB.http://dx.doi.org/10.1155/2021/5517856
spellingShingle José Alberto Choreño-Parra
Luis Armando Jiménez-Álvarez
Ellis Daniela Maldonado-Díaz
Graciela Cárdenas
Luis Alejandro Fernández-Lopez
José Luis Soto-Hernandez
Marcela Muñoz-Torrico
Gustavo Ramírez-Martínez
Alfredo Cruz-Lagunas
Armando Vega-López
María Lilia Domínguez-López
Carlos Sánchez-Garibay
Parménides Guadarrama-Ortíz
Silvia Giono
Luis Antonio Jiménez-Zamudio
Shabaana A. Khader
Ethel A. García-Latorre
Citlaltepetl Salinas-Lara
Joaquín Zúñiga
Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis
Journal of Immunology Research
title Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis
title_full Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis
title_fullStr Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis
title_full_unstemmed Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis
title_short Phenotype of Peripheral NK Cells in Latent, Active, and Meningeal Tuberculosis
title_sort phenotype of peripheral nk cells in latent active and meningeal tuberculosis
url http://dx.doi.org/10.1155/2021/5517856
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