IFN-γ Hinders Recovery from Mucosal Inflammation during Antibiotic Therapy for Salmonella Gut Infection.

Dolowschiak, Tamas; Mueller, Anna Angelika; Pisan, Lynn Joanna; Feigelman, Rounak; Felmy, Boas; Sellin, Mikael Erik; Namineni, Sukumar; Nguyen, Bidong Dinh; Wotzka, Sandra Yvonne; Heikenwalder, Mathias; von Mering, Christian; Müller, Christoph; Hardt, Wolf-Dietrich (2016). IFN-γ Hinders Recovery from Mucosal Inflammation during Antibiotic Therapy for Salmonella Gut Infection. Cell host & microbe, 20(2), pp. 238-249. Cell Press 10.1016/j.chom.2016.06.008

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Salmonella Typhimurium (S.Tm) causes acute enteropathy resolving after 4-7 days. Strikingly, antibiotic therapy does not accelerate disease resolution. We screened for factors blocking remission using a S.Tm enterocolitis model. The antibiotic ciprofloxacin clears pathogen stool loads within 3-24 hr, while gut pathology resolves more slowly (ψ50: ∼48 hr, remission: 6-9 days). This delayed resolution is mediated by an interferon-γ (IFN-γ)-dependent response that is triggered during acute infection and continues throughout therapy. Specifically, IFN-γ production by mucosal T and NK cells retards disease resolution by maintaining signaling through the transcriptional regulator STAT1 and boosting expression of inflammatory mediators like IL-1β, TNF, and iNOS. Additionally, sustained IFN-γ fosters phagocyte accumulation and hampers antimicrobial defense mediated by IL-22 and the lectin REGIIIβ. These findings reveal a role for IFN-γ in delaying resolution of intestinal inflammation and may inform therapies for acute Salmonella enteropathy, chronic inflammatory bowel diseases, or disease resolution during antibiotic treatment.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology

UniBE Contributor:

Müller, Christoph

ISSN:

1931-3128

Publisher:

Cell Press

Language:

English

Submitter:

Christa Hagert

Date Deposited:

23 Dec 2016 09:34

Last Modified:

27 Jul 2017 13:51

Publisher DOI:

10.1016/j.chom.2016.06.008

PubMed ID:

27453483

BORIS DOI:

10.7892/boris.91992

URI:

https://boris.unibe.ch/id/eprint/91992

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