A bacterial autotransporter impairs innate immune responses by targeting the transcription factor TFE3

Atri Ta, Rafael Ricci-Azevedo, Swathy O. Vasudevan, Skylar S. Wright, Puja Kumari, Morena S. Havira, Meera Surendran Nair, Vijay A. Rathinam, Sivapriya Kailasan Vanaja

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Type I interferons (IFNs) are consequential cytokines in antibacterial defense. Whether and how bacterial pathogens inhibit innate immune receptor-driven type I IFN expression remains mostly unknown. By screening a library of enterohemorrhagic Escherichia coli (EHEC) mutants, we uncovered EhaF, an uncharacterized protein, as an inhibitor of innate immune responses including IFNs. Further analyses identified EhaF as a secreted autotransporter—a type of bacterial secretion system with no known innate immune-modulatory function—that translocates into host cell cytosol and inhibit IFN response to EHEC. Mechanistically, EhaF interacts with and inhibits the MiT/TFE family transcription factor TFE3 resulting in impaired TANK phosphorylation and consequently, reduced IRF3 activation and type I IFN expression. Notably, EhaF-mediated innate immune suppression promotes EHEC colonization and pathogenesis in vivo. Overall, this study has uncovered a previously unknown autotransporter-based bacterial strategy that targets a specific transcription factor to subvert innate host defense.

Original languageEnglish (US)
Article number2035
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

All Science Journal Classification (ASJC) codes

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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