IFN-? Hinders Recovery from Mucosal Inflammation during Antibiotic Therapy for Salmonella Gut Infection
| Autor: | Anna Angelika Mueller, Sukumar Namineni, Tamas Dolowschiak, Lynn Joanna Pisan, Boas Felmy, Rounak Feigelman, Christian von Mering, Mathias Heikenwalder, Wolf-Dietrich Hardt, Mikael E. Sellin, Bidong Dinh Nguyen, Sandra Y. Wotzka, Christoph Mueller |
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| Rok vydání: | 2016 |
| Předmět: |
Salmonella typhimurium
0301 basic medicine Salmonella Phagocyte medicine.drug_class T-Lymphocytes Antibiotics Disease Biology medicine.disease_cause Microbiology Interferon-gamma 03 medical and health sciences Virology medicine Animals Immunologic Factors Enteropathy Intestinal Mucosa Pathogen Enterocolitis Phagocytes medicine.disease Anti-Bacterial Agents 3. Good health Gastrointestinal Tract Killer Cells Natural Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Salmonella Infections Immunology Parasitology Tumor necrosis factor alpha medicine.symptom Signal Transduction |
| Zdroj: | Cell Host & Microbe Cell Host & Microbe, 20 (2) Cell Host Microbe |
| DOI: | 10.1016/j.chom.2016.06.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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