Extracellular Vesicles from Pseudomonas aeruginosa Suppress MHC-Related Molecules in Human Lung Macrophages
Authors
Armstrong, David A.Lee, Min Kyung.
Hazlett, Haley F.
Dessaint, John A.
Mellinger, Diane L.
Aridgides, Daniel S.
Hendricks, Gregory M.
Abdalla, Moemen A. K.
Christensen, Brock C.
Ashare, Alix
UMass Chan Affiliations
Department of RadiologyDocument Type
Journal ArticlePublication Date
2020-08-20Keywords
Pseudomonas aeruginosapathogens
lungs
cystic fibrosis
macrophages
immune response
Bacteria
Bacterial Infections and Mycoses
Cell Biology
Immunology and Infectious Disease
Microbiology
Respiratory Tract Diseases
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Show full item recordAbstract
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.Source
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
DOI
10.4049/immunohorizons.2000026Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48456PubMed ID
32819967Related Resources
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Copyright © 2020 The Authors. This article is distributed under the terms of the CC BY-NC 4.0 Unported license.Distribution License
http://creativecommons.org/licenses/by-nc/4.0/ae974a485f413a2113503eed53cd6c53
10.4049/immunohorizons.2000026
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Except where otherwise noted, this item's license is described as Copyright © 2020 The Authors. This article is distributed under the terms of the CC BY-NC 4.0 Unported license.