Department of Radiology
Bacteria | Bacterial Infections and Mycoses | Cell Biology | Immunology and Infectious Disease | Microbiology | Respiratory Tract Diseases
Pseudomonas aeruginosa, a Gram-negative bacterium, is one of the most common pathogens colonizing the lungs of cystic fibrosis patients. P. aeruginosa secrete extracellular vesicles (EVs) that contain LPS and other virulence factors that modulate the host's innate immune response, leading to an increased local proinflammatory response and reduced pathogen clearance, resulting in chronic infection and ultimately poor patient outcomes. Lung macrophages are the first line of defense in the airway innate immune response to pathogens. Proper host response to bacterial infection requires communication between APC and T cells, ultimately leading to pathogen clearance. In this study, we investigate whether EVs secreted from P. aeruginosa alter MHC Ag expression in lung macrophages, thereby potentially contributing to decreased pathogen clearance. Primary lung macrophages from human subjects were collected via bronchoalveolar lavage and exposed to EVs isolated from P. aeruginosa in vitro. Gene expression was measured with the NanoString nCounter gene expression assay. DNA methylation was measured with the EPIC array platform to assess changes in methylation. P. aeruginosa EVs suppress the expression of 11 different MHC-associated molecules in lung macrophages. Additionally, we show reduced DNA methylation in a regulatory region of gene complement factor B (CFB) as the possible driving mechanism of widespread MHC gene suppression. Our results demonstrate MHC molecule downregulation by P. aeruginosa-derived EVs in lung macrophages, which is consistent with an immune evasion strategy employed by a prokaryote in a host-pathogen interaction, potentially leading to decreased pulmonary bacterial clearance.
Pseudomonas aeruginosa, pathogens, lungs, cystic fibrosis, macrophages, immune response
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Copyright © 2020 The Authors. This article is distributed under the terms of the CC BY-NC 4.0 Unported license.
DOI of Published Version
Armstrong DA, Lee MK, Hazlett HF, Dessaint JA, Mellinger DL, Aridgides DS, Hendricks GM, Abdalla MAK, Christensen BC, Ashare A. Extracellular Vesicles from Pseudomonas aeruginosa Suppress MHC-Related Molecules in Human Lung Macrophages. Immunohorizons. 2020 Aug 20;4(8):508-519. doi: 10.4049/immunohorizons.2000026. PMID: 32819967. Link to article on publisher's site
Armstrong DA, Lee MK, Hazlett HF, Dessaint JA, Mellinger DL, Aridgides DS, Hendricks GM, Abdalla MA, Christensen BC, Ashare A. (2020). Extracellular Vesicles from Pseudomonas aeruginosa Suppress MHC-Related Molecules in Human Lung Macrophages. Radiology Publications. https://doi.org/10.4049/immunohorizons.2000026. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/561
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