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 and Sivapriya Kailasan Vanaja ()
Additional contact information
Atri Ta: UConn Health School of Medicine
Rafael Ricci-Azevedo: UConn Health School of Medicine
Swathy O. Vasudevan: UConn Health School of Medicine
Skylar S. Wright: UConn Health School of Medicine
Puja Kumari: UConn Health School of Medicine
Morena S. Havira: Arvinas, Inc.
Meera Surendran Nair: Pennsylvania State University
Vijay A. Rathinam: UConn Health School of Medicine
Sivapriya Kailasan Vanaja: UConn Health School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37812-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37812-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37812-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().