ALTERATIONS OF THE LUNG ENVIRONMENT DURING A PNEUMONIA VIRUS OF MICE (PVM) INFECTION: STUDYING THE EFFECTS OF ALLERGEN INHALATION DURING AN UNDERLYING PVM INFECTION
Date
2019-09-30
Authors
Journal Title
Journal ISSN
Volume Title
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ORCID
0000-0002-9393-5678
Type
Thesis
Degree Level
Masters
Abstract
Respiratory syncytial virus (RSV) and other respiratory viruses are known for their implications in asthma exacerbation and development; many population-wide epidemiological studies indicate this correlation. Among children less than two years old, 99% have experienced an RSV infection, and about 36% of those children have also had a second infection. Due to this high frequency of RSV infections, infants also have a high chance of exposure to benign particulates before, during, and after a viral infection has peaked. There are many mouse models used to deduce immunological pathways leading to asthma development and exacerbation. I developed a model in mice where a natural route of allergen entry was utilized with another timeline of viral infection and allergen exposure. In this model, allergen exposure occurs during viral infection and after clearance; this realistically replicates a situation in children who are constantly exposed to benign allergens irrespective of their viral clearance status.
My model shows that if initial exposure occurs during a pneumonia virus of mice (PVM) infection, a secondary immune response towards cockroach allergen (CRA) is modified and becomes more inflammatory than if CRA exposure happens without any viral infection. Utilizing this model, we observed an increase in mucin mRNA (Gob5 and Muc5AC), as well as induction of IFN-γ, IL-4, and IL-10 mRNA and their corresponding cytokine proteins. Furthermore, we observed an increase in the influx of macrophages and dendritic cells in the lungs, indicating the presence of an inflammatory response towards CRA. Neutrophil and eosinophil influx within the bronchoalveolar lavage fluid and the lung tissue changed when mice were exposed to CRA during acute viral infection. This influx occurred despite the second exposure taking place after viral clearance and suggested a Th-2 skewed inflammatory response. IDO (indoleamine-2,3-dioxygenase)-1 expression was also enhanced towards CRA when the first exposure occurred during an underlying PVM infection. Thus, the overall response was stronger towards CRA than what CRA induced without an underlying PVM infection. This stronger response may correlate to the enhanced IDO-1 expression previously observed. Therefore, our data indicate that exposure to benign allergens during a respiratory infection can modify the response due to infection and produce a Th-2 type inflammatory response without additional eosinophil influx.
Description
Keywords
asthma, PVM, RSV, pneumonia virus of mice, respiratory syncytial virus
Citation
Degree
Master of Science (M.Sc.)
Department
Microbiology and Immunology
Program
Microbiology and Immunology