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

José Alberto Choreño-Parra,Ellis Daniela Maldonado-Díaz,María Lilia Domínguez-López,Graciela Cárdenas,Shabaana A Khader,Armando Vega-López,Gustavo Ramírez-Martínez,Marcela Muñoz-Torrico,Carlos Sánchez-Garibay,José Luís Soto-Hernández ,Luis Jiménez-Álvarez ,Luis Alejandro Fernández-López ,S Giono ,Citlaltépetl Salinas-Lara ,L Jiménez-Zamudio ,Parménides Guadarrama-Ortíz ,Ethel Garcı́a-Latorre ,Alfredo Cruz‐Lagunas ,Joaquı́n Zúñiga

doi:10.1155/2021/5517856

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.

Highlights

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the leading cause of death associated with a single pathogen [1]
Four patients in the tuberculous meningitis (TBM) group met the criteria for a definitive disease, as the infection was confirmed by positive culture of cerebrospinal fluid (CSF)
Most recruited participants with meningitis denied a history of pulmonary TB (PTB), and chest X-ray images obtained at hospital admission showed no lung involvement in six TBM patients

Summary

Introduction

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains the leading cause of death associated with a single pathogen [1]. The broad clinical spectrum of TB delays the diagnosis and initiation of antibiotic therapy, impeding an adequate control of Mtb transmission. In this regard, different clinical scenarios can result from human-Mtb interactions. 90% of infected humans with LTBI develop adaptive immune responses that control but do not eliminate Mtb, remaining asymptomatic. Another group of Mtb-infected individuals cannot establish or maintain protective immune mechanisms, progressing to active PTB. Most individuals manifest clinical data of Mtb infection limited to the lung, whereas in a small group of TB patients, the bacillus spreads to extrapulmonary organs [3]

Methods

Results

Conclusion