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A Bartonella effector acts as signaling hub for intrinsic STAT3 activation to trigger anti-inflammatory responses

Sorg, Isabel and Schmutz, Christoph and Lu, Yun-Yueh and Fromm, Katja and Siewert, Lena K. and Bögli, Alexandra and Strack, Kathrin and Harms, Alexander and Dehio, Christoph. (2020) A Bartonella effector acts as signaling hub for intrinsic STAT3 activation to trigger anti-inflammatory responses. Cell host & microbe, 27 (3). pp. 476-485.

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Official URL: https://edoc.unibas.ch/75737/

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Abstract

Chronically infecting pathogens avoid clearance by the innate immune system by promoting premature transition from an initial pro-inflammatory response toward an anti-inflammatory tissue-repair response. STAT3, a central regulator of inflammation, controls this transition and thus is targeted by numerous chronic pathogens. Here, we show that BepD, an effector of the chronic bacterial pathogen Bartonella henselae targeted to infected host cells, establishes an exceptional pathway for canonical STAT3 activation, thereby impairing secretion of pro-inflammatory TNF-α and stimulating secretion of anti-inflammatory IL-10. Tyrosine phosphorylation of EPIYA-related motifs in BepD facilitates STAT3 binding and activation via c-Abl-dependent phosphorylation of Y705. The tyrosine-phosphorylated scaffold of BepD thus represents a signaling hub for intrinsic STAT3 activation that is independent from canonical STAT3 activation via transmembrane receptor-associated Janus kinases. We anticipate that our findings on a molecular shortcut to STAT3 activation will inspire new treatment options for chronic infections and inflammatory diseases.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Dehio)
UniBasel Contributors:Dehio, Christoph and Sorg, Isabel and Siewert, Lena and Bögli, Alexandra Noëmi and Harms, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:1931-3128
e-ISSN:1934-6069
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:02 Apr 2020 13:24
Deposited On:02 Apr 2020 13:24

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