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
- Institución
- Instituto Nacional de Tecnología Agropecuaria
- OAI Identificador
- oai:localhost:20.500.12123/19058
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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)2025-09-29T13:46:46Zoai: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:l2025-09-29 13:46:46.525INTA 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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12.559606 |