Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells

Autores
Mansilla, Florencia Celeste; Miraglia, Maria Cruz; Maidana, Silvina Soledad; Randazzo, Cecilia Paola; Capozzo, Alejandra
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Innate immune cells show enhanced responsiveness to secondary challenges after an initial non-related stimulation (Trained Innate Immunity, TII). Acute NOD2 activation by Muramyl-Dipeptide (MDP) promotes TII inducing the secretion of pro-inflammatory mediators, while a sustained MDP-stimulation down-regulates the inflammatory response, restoring tolerance. Here we characterized in-vitro the response of murine macrophages to lipopolysaccharide (LPS) challenge under NOD2-chronic stimulation. RAW264.7 cells were trained with MDP (1 μg/ml, 48 h) and challenged with LPS (5 μg/ml, 24 h). Trained cells formed multinucleated giant cells with increased phagocytosis rates compared to untrained/challenged cells. They showed a reduced mitochondrial activity and a switch to aerobic glycolysis. TNF-α, ROS and NO were upregulated in both trained and untrained cultures (MDP+, MDP- cells, p > 0.05); while IL-10, IL-6 IL-12 and MHCII were upregulated only in trained cells after LPS challenge (MDP + LPS+, p < 0.05). A slight upregulation in the expression of B7.2 was also observed in this group, although differences were not statistically significant. MDP-training induced resistance to LPS challenge (p < 0.01). The relative expression of PARP-1 was downregulated after the LPS challenge, which may contribute to the regulatory milieu and to the innate memory mechanisms exhibited by MDP-trained cells. Our results demonstrate that a sustained MDP-training polarizes murine macrophages towards a M2b profile, inhibiting parthanatos. These results may impact on the development of strategies to immunomodulate processes in which inflammation should be controlled.
Instituto de Virología
Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Miraglia, María Cruz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Miraglia, María Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Maidana, Silvina Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Maidana, Silvina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Randazzo, Cecilia Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Capozzo, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Capozzo, Alejandra. Universidad Abierta Interamericana. Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS); Argentina
Fuente
Immunobiology 229 (5) : 152833 (September 2024)
Materia
Macrophages
Dipeptides
Lipopolysaccharides
Immunomodulation
Nucleotides
Macrófago
Dipéptido
Lipopolisacáridos
Inmunomodulación
Nucleótido
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/19058
Acceder
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oai_identifier_str oai:localhost:20.500.12123/19058
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cellsMansilla, Florencia CelesteMiraglia, Maria CruzMaidana, Silvina SoledadRandazzo, Cecilia PaolaCapozzo, AlejandraMacrophagesDipeptidesLipopolysaccharidesImmunomodulationNucleotidesMacrófagoDipéptidoLipopolisacáridosInmunomodulaciónNucleótidoInnate immune cells show enhanced responsiveness to secondary challenges after an initial non-related stimulation (Trained Innate Immunity, TII). Acute NOD2 activation by Muramyl-Dipeptide (MDP) promotes TII inducing the secretion of pro-inflammatory mediators, while a sustained MDP-stimulation down-regulates the inflammatory response, restoring tolerance. Here we characterized in-vitro the response of murine macrophages to lipopolysaccharide (LPS) challenge under NOD2-chronic stimulation. RAW264.7 cells were trained with MDP (1 μg/ml, 48 h) and challenged with LPS (5 μg/ml, 24 h). Trained cells formed multinucleated giant cells with increased phagocytosis rates compared to untrained/challenged cells. They showed a reduced mitochondrial activity and a switch to aerobic glycolysis. TNF-α, ROS and NO were upregulated in both trained and untrained cultures (MDP+, MDP- cells, p > 0.05); while IL-10, IL-6 IL-12 and MHCII were upregulated only in trained cells after LPS challenge (MDP + LPS+, p < 0.05). A slight upregulation in the expression of B7.2 was also observed in this group, although differences were not statistically significant. MDP-training induced resistance to LPS challenge (p < 0.01). The relative expression of PARP-1 was downregulated after the LPS challenge, which may contribute to the regulatory milieu and to the innate memory mechanisms exhibited by MDP-trained cells. Our results demonstrate that a sustained MDP-training polarizes murine macrophages towards a M2b profile, inhibiting parthanatos. These results may impact on the development of strategies to immunomodulate processes in which inflammation should be controlled.Instituto de VirologíaFil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Miraglia, María Cruz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Miraglia, María Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Maidana, Silvina Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Maidana, Silvina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Randazzo, Cecilia Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Capozzo, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Capozzo, Alejandra. Universidad Abierta Interamericana. Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS); ArgentinaElsevier2024-08-22T10:07:53Z2024-08-22T10:07:53Z2024-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/19058https://www.sciencedirect.com/science/article/pii/S01712985240005121878-32790171-2985https://doi.org/10.1016/j.imbio.2024.152833Immunobiology 229 (5) : 152833 (September 2024)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-10-16T09:31:49Zoai:localhost:20.500.12123/19058instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-10-16 09:31:49.656INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
title Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
spellingShingle Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
Mansilla, Florencia Celeste
Macrophages
Dipeptides
Lipopolysaccharides
Immunomodulation
Nucleotides
Macrófago
Dipéptido
Lipopolisacáridos
Inmunomodulación
Nucleótido
title_short Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
title_full Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
title_fullStr Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
title_full_unstemmed Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
title_sort Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
dc.creator.none.fl_str_mv Mansilla, Florencia Celeste
Miraglia, Maria Cruz
Maidana, Silvina Soledad
Randazzo, Cecilia Paola
Capozzo, Alejandra
author Mansilla, Florencia Celeste
author_facet Mansilla, Florencia Celeste
Miraglia, Maria Cruz
Maidana, Silvina Soledad
Randazzo, Cecilia Paola
Capozzo, Alejandra
author_role author
author2 Miraglia, Maria Cruz
Maidana, Silvina Soledad
Randazzo, Cecilia Paola
Capozzo, Alejandra
author2_role author
author
author
author
dc.subject.none.fl_str_mv Macrophages
Dipeptides
Lipopolysaccharides
Immunomodulation
Nucleotides
Macrófago
Dipéptido
Lipopolisacáridos
Inmunomodulación
Nucleótido
topic Macrophages
Dipeptides
Lipopolysaccharides
Immunomodulation
Nucleotides
Macrófago
Dipéptido
Lipopolisacáridos
Inmunomodulación
Nucleótido
dc.description.none.fl_txt_mv Innate immune cells show enhanced responsiveness to secondary challenges after an initial non-related stimulation (Trained Innate Immunity, TII). Acute NOD2 activation by Muramyl-Dipeptide (MDP) promotes TII inducing the secretion of pro-inflammatory mediators, while a sustained MDP-stimulation down-regulates the inflammatory response, restoring tolerance. Here we characterized in-vitro the response of murine macrophages to lipopolysaccharide (LPS) challenge under NOD2-chronic stimulation. RAW264.7 cells were trained with MDP (1 μg/ml, 48 h) and challenged with LPS (5 μg/ml, 24 h). Trained cells formed multinucleated giant cells with increased phagocytosis rates compared to untrained/challenged cells. They showed a reduced mitochondrial activity and a switch to aerobic glycolysis. TNF-α, ROS and NO were upregulated in both trained and untrained cultures (MDP+, MDP- cells, p > 0.05); while IL-10, IL-6 IL-12 and MHCII were upregulated only in trained cells after LPS challenge (MDP + LPS+, p < 0.05). A slight upregulation in the expression of B7.2 was also observed in this group, although differences were not statistically significant. MDP-training induced resistance to LPS challenge (p < 0.01). The relative expression of PARP-1 was downregulated after the LPS challenge, which may contribute to the regulatory milieu and to the innate memory mechanisms exhibited by MDP-trained cells. Our results demonstrate that a sustained MDP-training polarizes murine macrophages towards a M2b profile, inhibiting parthanatos. These results may impact on the development of strategies to immunomodulate processes in which inflammation should be controlled.
Instituto de Virología
Fil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Miraglia, María Cruz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Miraglia, María Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Maidana, Silvina Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Maidana, Silvina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Randazzo, Cecilia Paola. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina
Fil: Capozzo, Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Capozzo, Alejandra. Universidad Abierta Interamericana. Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS); Argentina
description Innate immune cells show enhanced responsiveness to secondary challenges after an initial non-related stimulation (Trained Innate Immunity, TII). Acute NOD2 activation by Muramyl-Dipeptide (MDP) promotes TII inducing the secretion of pro-inflammatory mediators, while a sustained MDP-stimulation down-regulates the inflammatory response, restoring tolerance. Here we characterized in-vitro the response of murine macrophages to lipopolysaccharide (LPS) challenge under NOD2-chronic stimulation. RAW264.7 cells were trained with MDP (1 μg/ml, 48 h) and challenged with LPS (5 μg/ml, 24 h). Trained cells formed multinucleated giant cells with increased phagocytosis rates compared to untrained/challenged cells. They showed a reduced mitochondrial activity and a switch to aerobic glycolysis. TNF-α, ROS and NO were upregulated in both trained and untrained cultures (MDP+, MDP- cells, p > 0.05); while IL-10, IL-6 IL-12 and MHCII were upregulated only in trained cells after LPS challenge (MDP + LPS+, p < 0.05). A slight upregulation in the expression of B7.2 was also observed in this group, although differences were not statistically significant. MDP-training induced resistance to LPS challenge (p < 0.01). The relative expression of PARP-1 was downregulated after the LPS challenge, which may contribute to the regulatory milieu and to the innate memory mechanisms exhibited by MDP-trained cells. Our results demonstrate that a sustained MDP-training polarizes murine macrophages towards a M2b profile, inhibiting parthanatos. These results may impact on the development of strategies to immunomodulate processes in which inflammation should be controlled.
publishDate 2024
dc.date.none.fl_str_mv 2024-08-22T10:07:53Z
2024-08-22T10:07:53Z
2024-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/19058
https://www.sciencedirect.com/science/article/pii/S0171298524000512
1878-3279
0171-2985
https://doi.org/10.1016/j.imbio.2024.152833
url http://hdl.handle.net/20.500.12123/19058
https://www.sciencedirect.com/science/article/pii/S0171298524000512
https://doi.org/10.1016/j.imbio.2024.152833
identifier_str_mv 1878-3279
0171-2985
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Immunobiology 229 (5) : 152833 (September 2024)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
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