Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS

Persons living with HIV (PLWH) are at higher risk of developing secondary illnesses than their uninfected counterparts, suggestive of a dysfunctional immune system in these individuals. Upon exposure to pathogens, monocytes undergo epigenetic remodeling that results in either a trained or a tolerant...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Celeste Faia, Karlie Plaisance-Bonstaff, Cecilia Vittori, Dorota Wyczechowska, Adam Lassak, Mary Meyaski-Schluter, Krzysztof Reiss, Francesca Peruzzi
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	HIV-1 Ikaros monocytes immune dysfunction endotoxin tolerance Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/57629db4da6d4e078ad15a2e03e3a73f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:57629db4da6d4e078ad15a2e03e3a73f
record_format	dspace
spelling	oai:doaj.org-article:57629db4da6d4e078ad15a2e03e3a73f2021-12-01T15:11:51ZAttenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS1664-322410.3389/fimmu.2021.785905https://doaj.org/article/57629db4da6d4e078ad15a2e03e3a73f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.785905/fullhttps://doaj.org/toc/1664-3224Persons living with HIV (PLWH) are at higher risk of developing secondary illnesses than their uninfected counterparts, suggestive of a dysfunctional immune system in these individuals. Upon exposure to pathogens, monocytes undergo epigenetic remodeling that results in either a trained or a tolerant phenotype, characterized by hyper-responsiveness or hypo-responsiveness to secondary stimuli, respectively. We utilized CD14+ monocytes from virally suppressed PLWH and healthy controls for in vitro analysis following polarization of these cells toward a pro-inflammatory monocyte-derived macrophage (MDM) phenotype. We found that in PLWH-derived MDMs, pro-inflammatory signals (TNFA, IL6, IL1B, miR-155-5p, and IDO1) dominate over negative feedback signals (NCOR2, GSN, MSC, BIN1, and miR-146a-5p), favoring an abnormally trained phenotype. The mechanism of this reduction in negative feedback involves the attenuated expression of IKZF1, a transcription factor required for de novo synthesis of RELA during LPS-induced inflammatory responses. Furthermore, restoring IKZF1 expression in PLWH-MDMs partially reinstated expression of negative regulators of inflammation and lowered the expression of pro-inflammatory cytokines. Overall, this mechanism may provide a link between dysfunctional immune responses and susceptibility to co-morbidities in PLWH with low or undetectable viral load.Celeste FaiaKarlie Plaisance-BonstaffCecilia VittoriDorota WyczechowskaAdam LassakMary Meyaski-SchluterKrzysztof ReissFrancesca PeruzziFrancesca PeruzziFrontiers Media S.A.articleHIV-1Ikarosmonocytesimmune dysfunctionendotoxin toleranceImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV-1 Ikaros monocytes immune dysfunction endotoxin tolerance Immunologic diseases. Allergy RC581-607
spellingShingle	HIV-1 Ikaros monocytes immune dysfunction endotoxin tolerance Immunologic diseases. Allergy RC581-607 Celeste Faia Karlie Plaisance-Bonstaff Cecilia Vittori Dorota Wyczechowska Adam Lassak Mary Meyaski-Schluter Krzysztof Reiss Francesca Peruzzi Francesca Peruzzi Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS
description	Persons living with HIV (PLWH) are at higher risk of developing secondary illnesses than their uninfected counterparts, suggestive of a dysfunctional immune system in these individuals. Upon exposure to pathogens, monocytes undergo epigenetic remodeling that results in either a trained or a tolerant phenotype, characterized by hyper-responsiveness or hypo-responsiveness to secondary stimuli, respectively. We utilized CD14+ monocytes from virally suppressed PLWH and healthy controls for in vitro analysis following polarization of these cells toward a pro-inflammatory monocyte-derived macrophage (MDM) phenotype. We found that in PLWH-derived MDMs, pro-inflammatory signals (TNFA, IL6, IL1B, miR-155-5p, and IDO1) dominate over negative feedback signals (NCOR2, GSN, MSC, BIN1, and miR-146a-5p), favoring an abnormally trained phenotype. The mechanism of this reduction in negative feedback involves the attenuated expression of IKZF1, a transcription factor required for de novo synthesis of RELA during LPS-induced inflammatory responses. Furthermore, restoring IKZF1 expression in PLWH-MDMs partially reinstated expression of negative regulators of inflammation and lowered the expression of pro-inflammatory cytokines. Overall, this mechanism may provide a link between dysfunctional immune responses and susceptibility to co-morbidities in PLWH with low or undetectable viral load.
format	article
author	Celeste Faia Karlie Plaisance-Bonstaff Cecilia Vittori Dorota Wyczechowska Adam Lassak Mary Meyaski-Schluter Krzysztof Reiss Francesca Peruzzi Francesca Peruzzi
author_facet	Celeste Faia Karlie Plaisance-Bonstaff Cecilia Vittori Dorota Wyczechowska Adam Lassak Mary Meyaski-Schluter Krzysztof Reiss Francesca Peruzzi Francesca Peruzzi
author_sort	Celeste Faia
title	Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS
title_short	Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS
title_full	Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS
title_fullStr	Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS
title_full_unstemmed	Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS
title_sort	attenuated negative feedback in monocyte-derived macrophages from persons living with hiv: a role for ikaros
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/57629db4da6d4e078ad15a2e03e3a73f
work_keys_str_mv	AT celestefaia attenuatednegativefeedbackinmonocytederivedmacrophagesfrompersonslivingwithhivaroleforikaros AT karlieplaisancebonstaff attenuatednegativefeedbackinmonocytederivedmacrophagesfrompersonslivingwithhivaroleforikaros AT ceciliavittori attenuatednegativefeedbackinmonocytederivedmacrophagesfrompersonslivingwithhivaroleforikaros AT dorotawyczechowska attenuatednegativefeedbackinmonocytederivedmacrophagesfrompersonslivingwithhivaroleforikaros AT adamlassak attenuatednegativefeedbackinmonocytederivedmacrophagesfrompersonslivingwithhivaroleforikaros AT marymeyaskischluter attenuatednegativefeedbackinmonocytederivedmacrophagesfrompersonslivingwithhivaroleforikaros AT krzysztofreiss attenuatednegativefeedbackinmonocytederivedmacrophagesfrompersonslivingwithhivaroleforikaros AT francescaperuzzi attenuatednegativefeedbackinmonocytederivedmacrophagesfrompersonslivingwithhivaroleforikaros AT francescaperuzzi attenuatednegativefeedbackinmonocytederivedmacrophagesfrompersonslivingwithhivaroleforikaros
_version_	1718404870725173248

Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS

Ejemplares similares