Model of Host-Pathogen Interaction Dynamics Links In Vivo Optical Imaging and Immune Responses.
Tracking disease progression in vivo is essential for the development of treatments against bacterial infection. Optical imaging has become a central tool for in vivo tracking of bacterial population development and therapeutic response. For a precise understanding of in vivo imaging results in terms of disease mechanisms derived from detailed postmortem observations, however, a link between the two is needed. Here, we develop a model that provides that link for the investigation of Citrobacter rodentium infection, a mouse model for enteropathogenic Escherichia coli (EPEC). We connect in vivo disease progression of C57BL/6 mice infected with bioluminescent bacteria, imaged using optical tomography and X-ray computed tomography, to postmortem measurements of colonic immune cell infiltration. We use the model to explore changes to both the host immune response and the bacteria and to evaluate the response to antibiotic treatment. The developed model serves as a novel tool for the identification and development of new therapeutic interventions.
Department of Life Sciences, Centre for Integrative Systems Biology, Imperial College London, London, United Kingdom.
Angelique
A
Ale
Department of Life Sciences, Medical Research Council (MRC) Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
Valerie F
VF
Crepin
Department of Life Sciences, Medical Research Council (MRC) Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
James W
JW
Collins
Department of Life Sciences, Medical Research Council (MRC) Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
Nicholas
N
Constantinou
Department of Life Sciences, Medical Research Council (MRC) Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
Maryam
M
Habibzay
Department of Life Sciences, Centre for Integrative Systems Biology, Imperial College London, London, United Kingdom.
Ann C
AC
Babtie
Department of Life Sciences, Medical Research Council (MRC) Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom g.frankel@imperial.ac.uk m.stumpf@imperial.ac.uk.
Gad
G
Frankel
Department of Life Sciences, Centre for Integrative Systems Biology, Imperial College London, London, United Kingdom g.frankel@imperial.ac.uk m.stumpf@imperial.ac.uk.
Michael P H
MPH
Stumpf
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D044082:Citrobacter rodentium / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D003106:Colon / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology*; D054308:Enteropathogenic Escherichia coli / Q000187:drug effects / Q000276:immunology* / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000276:immunology / Q000378:metabolism; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D061848:Optical Imaging / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000379:methods
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins
Citrobacter rodentium; antibiotic therapy; bioluminescent bacteria; dynamic modeling; espO mutant; in vivo imaging