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Visualization of the Charcoal Agar Resazurin Assay for Semi-quantitative, Medium-throughput Enumeration of Mycobacteria
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Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.

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  • 1Swiss Tropical and Public Health Institute, Allschwil, Switzerland.

European Journal of Immunology
|August 8, 2025
PubMed
Summary

Mycobacterium tuberculosis (Mtb) exploits granulomas for dormancy. Activated cytotoxic lymphocytes, specifically CD56+ cells and their granules containing granulysin, induce this Mtb dormancy, revealing a novel immune evasion strategy.

Keywords:
CyTOFMycobacterium tuberculosisNK cellsbacterial infectionscellular immunologycytotoxicitydormancygranulomagranulysinimmune evasion

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Area of Science:

  • Immunology
  • Microbiology
  • Pathogenesis

Background:

  • Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major global health issue.
  • Granulomas are key structures in TB pathogenesis, influencing infection outcomes.
  • Mtb persists in a dormant, antibiotic-tolerant state within granulomas, evading immune responses.

Purpose of the Study:

  • To identify immune factors within granulomas that drive Mtb dormancy.
  • To elucidate the mechanisms by which Mtb persists within the host.

Main Methods:

  • Generation of ex vivo granuloma-like structures from TB patient peripheral blood mononuclear cells.
  • High-dimensional mass cytometry to analyze immune cell populations and functions.
  • Direct exposure of Mtb to granulysin to assess dormancy induction.

Main Results:

  • Patient-derived granuloma-like structures induced Mtb dormancy ex vivo.
  • This dormancy correlated with an enrichment of activated innate cytotoxic lymphocytes.
  • CD56+ lymphocytes and their granule contents, particularly granulysin, were essential for inducing Mtb dormancy.

Conclusions:

  • Granulysin, released by CD56+ lymphocytes, directly induces Mtb dormancy.
  • This represents an immune escape mechanism where Mtb enters a dormant state to evade cytotoxic lymphocyte activity.