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Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
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Development and Assessment of Intracellular Infection Models for Staphylococcus aureus

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COMMD10-Guided Phagolysosomal Maturation Promotes Clearance of Staphylococcus aureus in Macrophages

Shani Ben Shlomo1, Odelia Mouhadeb2, Keren Cohen2

  • 1The Research Center for Digestive Tract and Liver Diseases, Tel-Aviv Sourasky Medical Center and Sackler School of Medicine, Tel-Aviv University, 6 Weizmann St, Tel-Aviv 64239, Israel.

Iscience
|April 9, 2019
PubMed

Insights

COMMD10 protein in macrophages is crucial for eliminating Staphylococcus aureus infections. Its deficiency impairs Kupffer cell function and phagolysosome maturation, hindering bacterial clearance.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Staphylococcus aureus is a significant human pathogen.
  • Kupffer cells (KCs) in the liver are vital for clearing S. aureus via phagocytosis.
  • The COMMD protein family regulates intracellular trafficking, but COMMD10's role in S. aureus eradication is unclear.

Purpose of the Study:

  • To investigate the role of COMMD10 in macrophage-mediated Staphylococcus aureus clearance.
  • To determine the impact of COMMD10 deficiency on phagolysosomal function during S. aureus infection.

Main Methods:

  • Utilized two different S. aureus subspecies for infection models.
  • Assessed S. aureus clearance in COMMD10-deficient macrophages and in vivo KCs.
  • Analyzed transcription factor EB activation, lysosomal biogenesis, and phagolysosomal maturation.
  • Examined the expression of the COMMD/CCDC22/CCDC93 complex.

Main Results:

  • COMMD10 deficiency in macrophages impaired timely S. aureus elimination.
  • COMMD10-deficient KCs showed reduced clearance of systemic S. aureus infection in vivo.
  • Macrophages lacking COMMD10 exhibited impaired transcription factor EB activation, leading to reduced lysosomal biogenesis.
  • Phagolysosomal maturation and function were significantly attenuated in COMMD10-deficient macrophages.
  • COMMD10 deficiency reduced the expression of the COMMD/CCDC22/CCDC93 complex.

Conclusions:

  • COMMD10 is essential for efficient Staphylococcus aureus eradication by macrophages.
  • COMMD10 plays a critical role in regulating macrophage phagolysosomal biogenesis and maturation.
  • COMMD10 influences the COMMD/CCDC22/CCDC93 complex, impacting bacterial clearance mechanisms.
Keywords:
Biological SciencesImmunologyMicrobiologyMolecular Microbiology

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