Understanding the Interplay of the Lung Microbiome on Pulmonary Inkt Cells in a Model of Allergic Asthma
Date
2022-05-05
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Abstract
The lung harbors a distinct population of bacteria in the upper and lower respiratory tracts referred to as the "Lung Microbiome" (LM), which interacts with resident innate immune cells. Although several studies have looked at LM changes in the context of disease, no group has fully conceptualized how perturbations in the LM can affect immune cell function in the lung. The first aim was to characterize and quantify changes within iNKT cells before and after perturbing the LM, in antibiotic treated and in germ free mice. In addition, the microbiome was explored within these same groups with 16S rDNA genome sequencing. The second aim was to address if early-life antibiotic treatment would result in increased disease severity, where the animals are challenged with the house dust mite model (HDM) of allergic asthma. I hypothesize that the local LM changes from birth to adulthood, will subsequently result in a shift of iNKT cell subsets proportions in order to fight a wide variety of diseases. If colonization is interrupted during the critical window of early life, then diseases can occur. I established that neonatal and germ-free mice have more pulmonary iNKT cells than colonized adult mice. Furthermore, perturbation of the microbiome with early-life antibiotics resulted in increased pulmonary iNKT cells, especially in neonatal mice. Additionally, early-life antibiotics treatment not only impacted iNKT cell phenotype but also increased disease severity after HDM challenge. In conclusion, a healthy LM may play a vital role in culling the pulmonary iNKT cells population in order to protect against chronic airway inflammation.
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Keywords
iNKT cells, Asthma
Citation
Sarkar, T. (2022). Understanding the Interplay of the Lung Microbiome on Pulmonary iNKT Cells in a Model of Allergic Asthma (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.