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Updated: Jul 15, 2025

Quantification of Cytosolic vs. Vacuolar Salmonella in Primary Macrophages by Differential Permeabilization
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Quantification of Cytosolic vs. Vacuolar Salmonella in Primary Macrophages by Differential Permeabilization

Published on: July 28, 2015

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p38MAPK/MK2 signaling stimulates host cells autophagy pathways to restrict Salmonella infection

Abdulhadi Suwandi1, Manoj B Menon2, Alexey Kotlyarov1

  • 1Institute of Cell Biochemistry, Hannover Medical School, Hannover, Germany.

Frontiers in Immunology
|September 29, 2023
PubMed

Insights

The p38 mitogen-activated protein kinase (MAPK)/MAPK-activated protein kinase 2 (MK2) pathway is crucial for host defense against Salmonella. Its inhibition impairs autophagy, increasing bacterial infection susceptibility.

Area of Science:

  • Cellular microbiology
  • Immunology
  • Molecular biology

Background:

  • Autophagy is a key cellular defense mechanism against intracellular pathogens like Salmonella.
  • The p38 mitogen-activated protein kinase (MAPK) pathway is implicated in cellular stress responses and immunity.

Purpose of the Study:

  • To investigate the role of the p38 MAPK/MK2 pathway in host cell susceptibility to Salmonella infection.
  • To elucidate the mechanisms by which p38 MAPK/MK2 influences Salmonella clearance via autophagy.

Main Methods:

  • Utilized Salmonella-infected mouse embryonic fibroblasts (MEFs) and MK2-deficient cells.
  • Employed western blot analysis to assess autophagy markers (LC3 lipidation) and key phosphorylation events (TANK-binding kinase-1, p62/SQTM1).
  • Conducted immunofluorescence microscopy to examine Salmonella colocalization with autophagy proteins (LC3, p62).
  • Assessed bacterial loads following autophagy inhibition with bafilomycin A1.

Main Results:

  • Inhibition of p38 MAPK or MK2 significantly increased Salmonella bacterial counts in MEFs.
  • MK2-deficient cells exhibited reduced LC3 lipidation, indicating impaired autophagy.
  • Lower phosphorylation of TANK-binding kinase-1 and p62/SQTM1 was observed in MK2-deficient cells, hindering p62 translocation and bacterial autophagy.
  • Reduced colocalization of Salmonella with LC3 and p62 was evident in MEFs lacking MK2.
  • Autophagy inhibition led to increased bacterial loads, confirming its role in controlling Salmonella.

Conclusions:

  • The p38 MAPK/MK2 pathway plays a critical role in modulating host cell defense against Salmonella infection.
  • p38 MAPK/MK2-mediated phosphorylation is essential for efficient autophagy of intracellular Salmonella by promoting key steps in the autophagy pathway.
  • Targeting the p38 MAPK/MK2 pathway could represent a novel therapeutic strategy to enhance host resistance to Salmonella.
Keywords:
MEFsMK2Salmonellaautophagycell signalinginfectionp38MAPKxenophagy

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