Artikel CC BY 4.0
referiert
Veröffentlicht

Aryl Hydrocarbon Receptor Activation by Benzo[a]pyrene Prevents Development of Septic Shock and Fatal Outcome in a Mouse Model of Systemic Salmonella enterica Infection

Zugehörigkeit
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Fueldner, Christiane;
Zugehörigkeit
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Riemschneider, Sina;
Zugehörigkeit
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Haupt, Janine;
ORCID
0000-0002-1854-5354
Zugehörigkeit
German Federal Institute for Risk Assessment (BfR), Department 7 - Chemical and Product Safety, Unit 77 - Product Analytics, Berlin, Germany
Jungnickel, Harald;
Zugehörigkeit
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Schulze, Felix;
Zugehörigkeit
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Zoldan, Katharina;
Zugehörigkeit
Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany
Esser, Charlotte;
Zugehörigkeit
Faculty of Life Sciences, University of Leipzig, Leipzig, Germany
Hauschildt, Sunna;
Zugehörigkeit
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Knauer, Jens;
ORCID
0000-0002-5866-901X
Zugehörigkeit
German Federal Institute for Risk Assessment (BfR), Department 7 - Chemical and Product Safety, Germany
Luch, Andreas;
Zugehörigkeit
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Kalkhof, Stefan;
Zugehörigkeit
Department of Preclinical Development and Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
Lehmann, Jörg

This study focused on immunomodulatory effects of aryl hydrocarbon receptor (AhR) activation through benzo[a]pyrene (BaP) during systemic bacterial infection. Using a well-established mouse model of systemic Salmonella enterica (S.E.) infection, we studied the influence of BaP on the cellular and humoral immune response and the outcome of disease. BaP exposure significantly reduced mortality, which is mainly caused by septic shock. Surprisingly, the bacterial burden in BaP-exposed surviving mice was significantly higher compared to non-exposed mice. During the early phase of infection (days 1–3 post-infection (p.i.)), the transcription of proinflammatory factors (i.e., IL-12, IFN-γ, TNF-α, IL-1β, IL-6, IL-18) was induced faster under BaP exposure. Moreover, BaP supported the activity of antigen-presenting cells (i.e., CD64 (FcγRI), MHC II, NO radicals, phagocytosis) at the site of infection. However, early in infection, the anti-inflammatory cytokines IL-10 and IL-22 were also locally and systemically upregulated in BaP-exposed S.E.-infected mice. BaP-exposure resulted in long-term persistence of salmonellae up to day 90 p.i., which was accompanied by significantly elevated S.E.-specific antibody responses (i.e., IgG1, IgG2c). In summary, these data suggest that BaP-induced AhR activation is capable of preventing a fatal outcome of systemic S.E. infection, but may result in long-term bacterial persistence, which, in turn, may support the development of chronic inflammation.

Vorschau

Zitieren

Zitierform:
Zitierform konnte nicht geladen werden.

Zugriffsstatistik

Gesamt:
Volltextzugriffe:
Metadatenansicht:
12 Monate:
Volltextzugriffe:
Metadatenansicht:

Rechte

Nutzung und Vervielfältigung: