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Inducible renitence limits Listeria monocytogenes escape from vacuoles in macrophages

Michael J Davis1, Brian Gregorka, Jason E Gestwicki

  • 1Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|September 25, 2012
PubMed

Insights

Macrophages possess a novel inducible defense mechanism, termed renitence, that strengthens endolysosomal membranes against damage. This protective activity, partly mediated by heat shock protein-70, enhances macrophage resistance to intracellular pathogens.

Area of Science:

  • Immunology
  • Cell Biology
  • Macrophage Biology

Background:

  • Endolysosomal membranes in macrophages are vulnerable to damage from phagocytosed particles and pathogen toxins.
  • Maintaining the integrity of these compartments is crucial for macrophage function and host defense.

Purpose of the Study:

  • To identify and characterize a novel inducible activity in macrophages that confers resistance to endolysosomal membrane damage.
  • To investigate the mechanisms underlying this protective response and its role in combating intracellular pathogens.

Main Methods:

  • Murine macrophages were pretreated with various stimuli (LPS, peptidoglycan, TNF-α, IFN-γ).
  • Membrane damage was induced using photooxidative chemistries or silica particles.
  • Pathogen escape assays (Listeria monocytogenes) were performed in wild-type and phagocyte oxidase-deficient macrophages.
  • The role of heat shock protein-70 was assessed.

Main Results:

  • Macrophage pretreatment induced an activity (renitence) protecting phagosomes, late endosomes, and lysosomes from membrane damage.
  • This protection was partially dependent on reactive oxygen species but independent of phagocyte oxidase.
  • IFN-γ-stimulated macrophages showed inhibited Listeria monocytogenes escape, indicating a role in pathogen resistance.
  • Heat shock protein-70 was partially responsible for both renitence and pathogen escape inhibition.

Conclusions:

  • Macrophages possess an inducible renitence activity that safeguards endolysosomal membrane integrity.
  • This novel defense mechanism contributes to macrophage resistance against intracellular pathogens that compromise intracellular membranes.
  • Heat shock protein-70 plays a significant role in mediating this inducible protective response.

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