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P62 inhibits IL-1β release during Salmonella Typhimurium infection of macrophages

Nina Judith Hos1,2,3, Julia Fischer2,3,4,5,6, Ambika M V Murthy7,8

  • 1Institute for Medical Microbiology, Immunology and Hygiene, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Frontiers in Cellular and Infection Microbiology
|April 25, 2025
PubMed

Insights

The protein p62 (Sequestome-1) limits excessive inflammation during Salmonella Typhimurium infection by promoting the autophagic degradation of inflammasome components, balancing key immune signaling pathways.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Macrophages are crucial for innate immunity against Salmonella Typhimurium.
  • Salmonella Typhimurium infection activates NLRC3 and NLRP4 inflammasomes, leading to IL-1β secretion.
  • Autophagy is implicated in limiting inflammation by degrading inflammasomes.

Purpose of the Study:

  • To investigate the role of the autophagic adaptor p62 (Sequestome-1) in regulating inflammasome activation during Salmonella Typhimurium infection.
  • To understand how p62 influences inflammatory cytokine secretion in macrophages.

Main Methods:

  • Macrophage infection models with Salmonella Typhimurium.
  • Analysis of inflammasome activation and cytokine secretion (IL-1β, IL-10, IFN-β).
  • Assessment of autophagy pathways and the role of p62 in targeting ASC for degradation.

Main Results:

  • p62 restricts inflammasome availability and IL-1β secretion in macrophages infected with Salmonella Typhimurium.
  • Loss of p62 impairs autophagy, leading to increased secretion of IL-1β, IL-10, and IFN-β.
  • p62 targets the inflammasome adaptor ASC for autophagic degradation.

Conclusions:

  • p62 plays a novel role in inducing autophagy to control inflammasome activation.
  • p62 balances pro- and anti-inflammatory signaling pathways, preventing excessive inflammation during Salmonella Typhimurium infection.
Keywords:
ASCIFN-IIFN-βIL-10IL-1βautophagyinflammasomep62

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