PRAK Promotes the Pathogen Clearance by Macrophage Through Regulating Autophagy and Inflammasome Activation

Ligu Mi1,2, Yan Wang1, Hui Xu3

  • 1Department of Immunology, School of Basic Medical Sciences, National Health Commission (NHC) Key Laboratory of Medical Immunology, Peking University, Beijing, China.

Insights

The p38 regulated/activated protein kinase (PRAK) is crucial for macrophage function in fighting infections. PRAK deficiency impairs bacterial clearance and increases susceptibility to pathogens like Listeria monocytogenes.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • p38 regulated/activated protein kinase (PRAK) is a downstream kinase of p38MAPK.
  • The role of PRAK in macrophage function remains largely unexplored.

Purpose of the Study:

  • To investigate the function of PRAK in macrophages.
  • To determine PRAK's role in host defense against intracellular pathogens.

Main Methods:

  • Generated myeloid-specific Prak-deficient mice.
  • Assessed macrophage populations, phenotype, and function.
  • Infected mice with Listeria monocytogenes and evaluated host survival, bacterial load, and cytokine levels.
  • Investigated ROS production, inflammasome activation, and autophagy in Prak-deficient macrophages.

Main Results:

  • Myeloid-specific Prak deletion reduced peritoneal macrophages (F4/80+CD11b+) with decreased MHC-II and CD80 expression.
  • Prak-deficient mice exhibited increased mortality, higher bacterial burden, and elevated proinflammatory cytokines after L. monocytogenes infection.
  • Prak-deficient macrophages showed impaired bactericidal activity, defective ROS production, inflammasome activation, and autophagy.

Conclusions:

  • PRAK is essential for macrophage-mediated clearance of intracellular pathogens.
  • PRAK influences multiple macrophage functions, including phagocytosis, bacterial killing, ROS generation, inflammasome activation, and autophagy.
  • PRAK plays a critical role in the innate immune response to bacterial infection.

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