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Pseudomonas aeruginosa-derived DnaJ functions as a novel immunomodulator inducing IFNβ via CME-SGK1-IRF3 axis in

Jaehoo Lee1,2, Yeji Lee1, Yongxin Jin3

  • 1Department of Biotechnology and Bioinformatics, Korea University, Sejong, 30019, Republic of Korea.

Scientific Reports
|December 3, 2025
PubMed

Insights

Pseudomonas aeruginosa DnaJ, a heat shock protein 40 (HSP40), potently induces type I interferon beta (IFNβ) expression in macrophages. This discovery offers potential for new immunotherapies against bacterial infections.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Type I interferons (IFNs), especially IFNβ, are crucial for immune responses to microbial infections.
  • Pseudomonas aeruginosa (P. aeruginosa) can induce IFNβ, but the specific bacterial factors are largely unknown.

Purpose of the Study:

  • To identify microbial factors from P. aeruginosa that induce IFNβ expression in macrophages.
  • To elucidate the molecular mechanisms underlying DnaJ-mediated IFNβ induction.

Main Methods:

  • Screening of bacterial heat shock protein 40 (HSP40) homologs for IFNβ induction.
  • Investigating the signaling pathways involved, including Toll-like receptor 4 (TLR4), TRIF-TBK1-IRF3, and clathrin-mediated endocytosis (CME).
  • Assessing the role of serum/glucocorticoid regulated kinase 1 (SGK1) in the pathway.

Main Results:

  • P. aeruginosa DnaJ was identified as a potent inducer of IFNβ production in macrophages.
  • DnaJ-induced IFNβ expression relies on the TLR4-TRIF-TBK1-IRF3 signaling axis.
  • Clathrin-mediated endocytosis and SGK1 are essential for DnaJ-mediated IRF3 activation and subsequent IFNβ expression.
  • Human HSP40 utilizes a similar CME-SGK1-IRF3 pathway to induce IFNβ.

Conclusions:

  • P. aeruginosa DnaJ is a novel microbial inducer of IFNβ.
  • The identified pathway (CME-SGK1-IRF3) is conserved between bacterial and human HSP40.
  • DnaJ presents a potential therapeutic target for modulating innate immunity or as an adjuvant in immunotherapy.
Keywords:
Pseudomonas aeruginosaCMEDnaJIFNβIRF3SGK1

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