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IFN-γ Hinders Recov...
IFN-γ Hinders Recovery from Mucosal Inflammation during Antibiotic Therapy for Salmonella Gut Infection.
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Dolowschiak, Tamas (author)
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Mueller, Anna Angelika (author)
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Pisan, Lynn Joanna (author)
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Feigelman, Rounak (author)
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Felmy, Boas (author)
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Sellin, Mikael Erik (author)
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Namineni, Sukumar (author)
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Nguyen, Bidong Dinh (author)
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Wotzka, Sandra Yvonne (author)
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Heikenwalder, Mathias (author)
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von Mering, Christian (author)
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Mueller, Christoph (author)
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Hardt, Wolf-Dietrich (author)
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- Elsevier BV, 2016
- 2016
- English.
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In: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 20:2
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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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.
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- By the author/editor
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Dolowschiak, Tam ...
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Mueller, Anna An ...
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Pisan, Lynn Joan ...
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Feigelman, Rouna ...
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Felmy, Boas
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Sellin, Mikael E ...
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show more...
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Namineni, Sukuma ...
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Nguyen, Bidong D ...
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Wotzka, Sandra Y ...
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Heikenwalder, Ma ...
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von Mering, Chri ...
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Mueller, Christo ...
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Hardt, Wolf-Diet ...
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show less...
- Articles in the publication
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Cell Host and Mi ...
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Uppsala University