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Non-Invasive Luciferase Imaging of Type I Interferon Induction in a Transgenic Mouse Model of Biomaterial Associated Bacterial Infections: Microbial Specificity and Inter-Bacterial Species Interactions

Authors
  • Rahim, Muhammad Imran1, 2
  • Winkel, Andreas1, 2
  • Lienenklaus, Stefan
  • Stumpp, Nico S.1, 2
  • Szafrański, Szymon P.1, 2
  • Kommerein, Nadine1, 2
  • Willbold, Elmar2, 3
  • Reifenrath, Janin2, 3
  • Mueller, Peter P.
  • Eisenburger, Michael1
  • Stiesch, Meike1, 2
  • 1 (M.S.)
  • 2 (J.R.)
  • 3 Department of Orthopedic Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
Type
Published Article
Journal
Microorganisms
Publisher
MDPI AG
Publication Date
Oct 21, 2020
Volume
8
Issue
10
Identifiers
DOI: 10.3390/microorganisms8101624
PMID: 33096869
PMCID: PMC7589032
Source
PubMed Central
Keywords
License
Green

Abstract

The performance of biomaterials is often compromised by bacterial infections and subsequent inflammation. So far, the conventional analysis of inflammatory processes in vivo involves time-consuming histology and biochemical assays. The present study employed a mouse model where interferon beta (IFN-β) is monitored as a marker for non-invasive rapid detection of inflammation in implant-related infections. The mouse model comprises subcutaneous implantation of morphologically modified titanium, followed by experimental infections with four taxonomically diverse oral bacteria: Streptococcus oralis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Treponema denticola (as mono culture or selected mixed-culture). IFN-β expression increased upon infections depending on the type of pathogen and was prolonged by the presence of the implant. IFN-β expression kinetics reduced with two mixed species infections when compared with the single species. Histological and confocal microscopy confirmed pathogen-specific infiltration of inflammatory cells at the implant-tissue interface. This was observed mainly in the vicinity of infected implants and was, in contrast to interferon expression, higher in infections with dual species. In summary, this non-invasive mouse model can be used to quantify longitudinally host inflammation in real time and suggests that the polymicrobial character of infection, highly relevant to clinical situations, has complex effects on host immunity.

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