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

José Alberto Choreño-Parra1,2, Luis Armando Jiménez-Álvarez1,2, Ellis Daniela Maldonado-Díaz3

  • 1Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Inmunoquímica I, Mexico City, Mexico.

Journal of Immunology Research
|May 19, 2021
PubMed

Insights

Natural killer (NK) cells show reduced frequency and impaired memory-like responses in tuberculous meningitis (TBM) patients. These findings highlight a distinct NK cell profile in TBM, differing from latent and pulmonary tuberculosis.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Tuberculosis Research

Background:

  • Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) with poorly understood immunopathology.
  • Mycobacterium tuberculosis (Mtb) spread is thought to occur early, before adaptive immunity, implicating innate mechanisms in disease containment.
  • Natural killer (NK) cells are known to differentiate latent TB infection (LTBI) from active pulmonary TB (PTB), but their role in TBM remains unclear.

Purpose of the Study:

  • To investigate the phenotype and function of circulating NK cells in TBM patients.
  • To compare NK cell responses in TBM patients with those in LTBI and PTB individuals.
  • To explore the role of NK cells in the immunopathology of TBM.

Main Methods:

  • Cross-sectional analysis of circulating NK cell phenotype in TBM patients using flow cytometry.
  • In vitro assessment of memory-like NK cell subpopulation responses to Mtb antigens.
  • Quantification of plasma soluble NKG2D receptor ligands via ELISA.

Main Results:

  • TBM patients exhibited lower absolute NK cell frequencies and higher CD69 expression compared to LTBI individuals.
  • A diminished expansion of the CD45RO+ memory-like NK cell subpopulation was observed in TBM patients upon Mtb exposure.
  • TBM patients showed a reduced frequency of CD56brightCD16- NK cells, a characteristic not seen in LTBI or PTB subjects.
  • Frequencies of cytokine-producing NK cells were lower in TBM patients compared to both LTBI and PTB groups.

Conclusions:

  • NK cell profiles in TBM patients are distinct, characterized by reduced frequencies and impaired memory-like responses.
  • The findings suggest a potentially compromised role of NK cells in controlling Mtb infection in the context of TBM.
  • Further research into NK cell-mediated immunity could offer new therapeutic targets for TBM management.

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