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Interaction of mycobacteria with Plasmin(ogen) affects phagocytosis and granuloma development

Gabriela Echeverría-Valencia1, Mayra Silva-Miranda2, Euloge Ekaza3

  • 1Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70-228, México D.F, 04510, Mexico.

Tuberculosis (Edinburgh, Scotland)
|August 6, 2019
PubMed

Insights

Mycobacterium bovis BCG coated with plasminogen or plasmin reduced macrophage phagocytosis but initially increased granuloma formation. Ultimately, plasmin(ogen) on BCG led to more bacteria within granulomas.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Plasminogen and plasmin are key fibrinolytic system components with immunopathological roles.
  • Mycobacterium tuberculosis interactions with plasminogen are known, but effects on Mycobacterium bovis BCG are less understood.

Purpose of the Study:

  • To investigate the impact of plasminogen/plasmin bound to Mycobacterium bovis BCG on macrophage phagocytosis and in vitro human granuloma formation.
  • To determine how BCG-bound plasminogen/plasmin influences cytokine secretion and bacterial load within granulomas.

Main Methods:

  • Coating Mycobacterium bovis BCG with plasminogen and plasmin (activated by tissue plasminogen activator).
  • Assessing phagocytosis by THP1 macrophages.
  • Evaluating granuloma formation, development, and bacterial presence in an in vitro human granuloma model.
  • Measuring Interleukin-6 (IL-6) secretion.

Main Results:

  • BCG coated with plasminogen or plasmin showed significantly reduced phagocytosis by macrophages.
  • At 3 days, BCG with plasminogen/plasmin increased granuloma numbers and IL-6 secretion compared to uncoated BCG.
  • By 7 days, fewer granulomas and more bacteria were observed with BCG/plasminogen/plasmin compared to uncoated BCG.

Conclusions:

  • Plasminogen/plasmin on the mycobacterial surface modulates macrophage phagocytosis.
  • BCG-bound plasminogen/plasmin influences granuloma development and the cytokine environment.
  • These interactions ultimately lead to an increased bacterial burden within granulomas, suggesting a role in mycobacterial pathogenesis.
Keywords:
BCGFibrinolytic systemGranulomaMycobacteriumPlasminPlasminogenTuberculosis

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