Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells
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...
| Autores principales: | , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
Elsevier
2024
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| Acceso en línea: | 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 |
| _version_ | 1855486292219920384 |
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| author | Mansilla, Florencia Celeste Miraglia, Maria Cruz Maidana, Silvina Soledad Randazzo, Cecilia Paola Capozzo, Alejandra |
| author_browse | Capozzo, Alejandra Maidana, Silvina Soledad Mansilla, Florencia Celeste Miraglia, Maria Cruz Randazzo, Cecilia Paola |
| author_facet | Mansilla, Florencia Celeste Miraglia, Maria Cruz Maidana, Silvina Soledad Randazzo, Cecilia Paola Capozzo, Alejandra |
| author_sort | Mansilla, Florencia Celeste |
| collection | INTA Digital |
| 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. |
| format | Artículo |
| id | INTA19058 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | INTA190582024-08-22T10:15:19Z Chronic NOD2 stimulation by MDP confers protection against parthanatos through M2b macrophage polarization in RAW264.7 cells Mansilla, Florencia Celeste Miraglia, Maria Cruz Maidana, Silvina Soledad Randazzo, Cecilia Paola Capozzo, Alejandra Macrophages Dipeptides Lipopolysaccharides Immunomodulation Nucleotides Macrófago Dipéptido Lipopolisacáridos Inmunomodulación Nucleótido 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 2024-08-22T10:07:53Z 2024-08-22T10:07:53Z 2024-09 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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) application/pdf Elsevier Immunobiology 229 (5) : 152833 (September 2024) |
| spellingShingle | Macrophages Dipeptides Lipopolysaccharides Immunomodulation Nucleotides Macrófago Dipéptido Lipopolisacáridos Inmunomodulación Nucleótido Mansilla, Florencia Celeste Miraglia, Maria Cruz Maidana, Silvina Soledad Randazzo, Cecilia Paola Capozzo, Alejandra 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 |
| 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_short | 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 |
| topic | Macrophages Dipeptides Lipopolysaccharides Immunomodulation Nucleotides Macrófago Dipéptido Lipopolisacáridos Inmunomodulación Nucleótido |
| 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 |
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