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Host-Microbiome Interactions Influence Pulmonary Disease Development

thesis
posted on 01.05.2021, 00:00 by Cody Adam Schott
The human microbiome, defined as the communities of microorganisms that inhabit various bodily niches, has been considered a novel essential organ system. Prior work has identified links between colonizing organisms, innate immunity and adaptive immunity in the regulation of inflammatory processes. The lungs, previously thought to be devoid of commensal organisms, represent a novel target for microbiome research given their environmental exposure. The analyses performed in this work sought to delineate the role of host-microbiome interactions in sarcoidosis and bronchiolitis obliterans syndrome (BOS), two respiratory diseases with poorly defined etiologies. In sarcoidosis, deficient expression of genes associated with lymphocyte mediated immunity was associated with disease progression and loss of pulmonary function, despite increased expression of cytokine and interferon response elements. Strikingly, expression of these pathways was linked to systemic exposure of Streptococcaceae, Sphingomonadaceae, and Burkholderiaceae families. Additionally, airway exposure to Micrococcaceae was associated with increased lymphocyte counts in newly diagnosed sarcoidosis patients. In the study of BOS, an airway microbiome phenotype composed largely of gram-positive organisms promoted resilience towards BOS in lung transplant populations. This phenotype was associated with reduced airway inflammation and reduced neutrophilic infiltration of the airway. Collectively, these analyses suggest that microbial exposures influence innate and adaptive immunity in the lung, promoting or protecting against pathogenesis and disease progression.

History

Advisor

Finn, Patricia WPerkins, David L

Chair

Freitag, Nancy

Department

Microbiology and Immunology

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

McLachlan, Alan Sun, Jun Dudek, Steven

Submitted date

May 2021

Thesis type

application/pdf

Language

en