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

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

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Abstract

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.

Original languageEnglish
Article number5517856
JournalJournal of Immunology Research
Volume2021
DOIs
StatePublished - 2021

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