Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation

Abstract Objectives Sepsis is defined as the host's inflammatory response to a life‐threatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macroli...

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Autores principales:	Stéphanie Pons, Eden Arrii, Marine Arnaud, Maud Loiselle, Juliette Ferry, Manel Nouacer, Julien Lion, Shannon Cohen, Nuala Mooney, Lara Zafrani
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	antibiotics endothelium immunoregulation septic shock inflammation Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/2d6405c662544f71bfa0f420c3450e13
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spelling	oai:doaj.org-article:2d6405c662544f71bfa0f420c3450e132021-11-12T19:57:15ZImmunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation2050-452710.1002/iid3.518https://doaj.org/article/2d6405c662544f71bfa0f420c3450e132021-12-01T00:00:00Zhttps://doi.org/10.1002/iid3.518https://doaj.org/toc/2050-4527Abstract Objectives Sepsis is defined as the host's inflammatory response to a life‐threatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macrolides can exert immunomodulation of endothelial cells (ECs) in an experimental model of sepsis. Methods Human ECs were stimulated by proinflammatory cytokines and lipopolysaccharide before exposure to macrolides. ECs phenotypes were analyzed by flow cytometry. Cocultures of ECs and peripheral blood mononuclear cells (PBMCs) were performed to study the ECs ability to alter T‐cell viability and differentiation in the presence of macrolides. Soluble factor production was assessed. Results ECs act as non‐professional antigen presenting cells and expressed human leukocyte antigen (HLA) antigens, the adhesion molecules CD54, CD106, and the coinhibitory molecule CD274 after septic stimulation. Incubation with macrolides induced a significant decrease of HLA class I and HLA class II HLA‐DR on septic‐stimulated ECs, but did not alter either CD54, CD106, nor CD274 expression. Interleukin‐6 (IL‐6) and IL‐8 production by stimulated ECs were unaltered by incubation with macrolides, whereas Clarithromycin exposure significantly decreased IL‐6 gene expression. In cocultures of septic ECs with PBMCs, neither the proportion of CD4 + , CD8 + T nor their viability was altered by macrolides. T‐helper lymphocyte subsets Th1, Th17, and Treg polarization by stimulated ECs were unaltered by macrolides. Conclusion This study reports phenotypic and gene expression changes in septic‐stimulated ECs exposed to macrolides, without resulting in altered immunogenicity of ECs in co‐cultures with PBMCs. In vivo studies may help to further understand the impact of macrolide therapy on ECs immune homeostasis during sepsis.Stéphanie PonsEden ArriiMarine ArnaudMaud LoiselleJuliette FerryManel NouacerJulien LionShannon CohenNuala MooneyLara ZafraniWileyarticleantibioticsendotheliumimmunoregulationseptic shockinflammationImmunologic diseases. AllergyRC581-607ENImmunity, Inflammation and Disease, Vol 9, Iss 4, Pp 1656-1669 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotics endothelium immunoregulation septic shock inflammation Immunologic diseases. Allergy RC581-607
spellingShingle	antibiotics endothelium immunoregulation septic shock inflammation Immunologic diseases. Allergy RC581-607 Stéphanie Pons Eden Arrii Marine Arnaud Maud Loiselle Juliette Ferry Manel Nouacer Julien Lion Shannon Cohen Nuala Mooney Lara Zafrani Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation
description	Abstract Objectives Sepsis is defined as the host's inflammatory response to a life‐threatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macrolides can exert immunomodulation of endothelial cells (ECs) in an experimental model of sepsis. Methods Human ECs were stimulated by proinflammatory cytokines and lipopolysaccharide before exposure to macrolides. ECs phenotypes were analyzed by flow cytometry. Cocultures of ECs and peripheral blood mononuclear cells (PBMCs) were performed to study the ECs ability to alter T‐cell viability and differentiation in the presence of macrolides. Soluble factor production was assessed. Results ECs act as non‐professional antigen presenting cells and expressed human leukocyte antigen (HLA) antigens, the adhesion molecules CD54, CD106, and the coinhibitory molecule CD274 after septic stimulation. Incubation with macrolides induced a significant decrease of HLA class I and HLA class II HLA‐DR on septic‐stimulated ECs, but did not alter either CD54, CD106, nor CD274 expression. Interleukin‐6 (IL‐6) and IL‐8 production by stimulated ECs were unaltered by incubation with macrolides, whereas Clarithromycin exposure significantly decreased IL‐6 gene expression. In cocultures of septic ECs with PBMCs, neither the proportion of CD4 + , CD8 + T nor their viability was altered by macrolides. T‐helper lymphocyte subsets Th1, Th17, and Treg polarization by stimulated ECs were unaltered by macrolides. Conclusion This study reports phenotypic and gene expression changes in septic‐stimulated ECs exposed to macrolides, without resulting in altered immunogenicity of ECs in co‐cultures with PBMCs. In vivo studies may help to further understand the impact of macrolide therapy on ECs immune homeostasis during sepsis.
format	article
author	Stéphanie Pons Eden Arrii Marine Arnaud Maud Loiselle Juliette Ferry Manel Nouacer Julien Lion Shannon Cohen Nuala Mooney Lara Zafrani
author_facet	Stéphanie Pons Eden Arrii Marine Arnaud Maud Loiselle Juliette Ferry Manel Nouacer Julien Lion Shannon Cohen Nuala Mooney Lara Zafrani
author_sort	Stéphanie Pons
title	Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation
title_short	Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation
title_full	Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation
title_fullStr	Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation
title_full_unstemmed	Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation
title_sort	immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/2d6405c662544f71bfa0f420c3450e13
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Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation

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