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Published on: August 17, 2018
Infection of Human Precision-Cut Lung Slices with the Influenza Virus
Katherina Sewald1, Olga Danov2
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany. katherina.sewald@item.fraunhofer.de.
Abstract:
Viral infections are common causes of asthma exacerbations. To model these processes ex vivo, human precision-cut lung slices (PCLSs) can be used. Here we describe the infection of human PCLSs with the human influenza virus. We then provide methods to quantify the virus and reveal its localization within infected PCLSs and study consequences of infection, including cell death and production of cytokines, chemokine, and mucus. We also describe the stimulation of PCLSs with immune mediators such as pro-inflammatory tumor necrosis factor α (TNF-α). These models are useful to investigate mechanisms of virally induced asthma exacerbations and study modes of action and efficacy of antiviral and/or anti-inflammatory drugs.
Insights
Human lung tissue models (PCLSs) infected with influenza virus reveal infection mechanisms. This research aids in understanding viral asthma exacerbations and testing new drugs.
Area of Science:
- * Respiratory viral infections and immunology.
- * Infectious disease modeling.
- * Pharmacological research.
Background:
- * Viral infections frequently trigger asthma exacerbations.
- * Ex vivo models are crucial for studying these complex interactions.
- * Human precision-cut lung slices (PCLSs) offer a relevant model system.
Purpose of the Study:
- * To establish and validate a human PCLS model for influenza virus infection.
- * To investigate viral localization and host responses within the lung tissue.
- * To assess the utility of this model for evaluating antiviral and anti-inflammatory therapies.
Main Methods:
- * Infection of human PCLSs with human influenza virus.
- * Quantification of viral load and determination of viral localization using microscopy.
- * Analysis of host responses, including cell death, cytokine, chemokine, and mucus production.
- * Stimulation of PCLSs with immune mediators like tumor necrosis factor α (TNF-α).
Main Results:
- * Successful infection of human PCLSs with influenza virus was achieved.
- * Methods were established to quantify virus and determine its location within lung tissue.
- * Consequences of infection, including cellular damage and inflammatory mediator release, were characterized.
- * The model responded to immune mediators like TNF-α.
Conclusions:
- * Human PCLSs provide a robust ex vivo model for studying influenza virus infection in the lung.
- * This model allows for detailed investigation of viral pathogenesis and host responses relevant to asthma.
- * The PCLS model is valuable for preclinical assessment of antiviral and anti-inflammatory drug efficacy.
