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

Autor: Mansilla FC; Institute of Virology and Technological Innovations, Center for Research in Veterinary and Agronomic Sciences (CICVyA), INTA, Buenos Aires, Argentina. Electronic address: mansilla.florencia@inta.gob.ar., Miraglia MC; Institute of Virology and Technological Innovations, Center for Research in Veterinary and Agronomic Sciences (CICVyA), INTA, Buenos Aires, Argentina; National Council for Scientific and Technical Research (CONICET)., Maidana SS; Institute of Virology and Technological Innovations, Center for Research in Veterinary and Agronomic Sciences (CICVyA), INTA, Buenos Aires, Argentina; National Council for Scientific and Technical Research (CONICET)., Cecilia R; Institute of Virology and Technological Innovations, Center for Research in Veterinary and Agronomic Sciences (CICVyA), INTA, Buenos Aires, Argentina., Capozzo AV; National Council for Scientific and Technical Research (CONICET); Center for Advanced Studies in Human Sciences and Health (CAECIHS), Interamerican Open University (UAI), Buenos Aires, Argentina.
Jazyk: angličtina
Zdroj: Immunobiology [Immunobiology] 2024 Sep; Vol. 229 (5), pp. 152833. Date of Electronic Publication: 2024 Jun 29.
DOI: 10.1016/j.imbio.2024.152833
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze: MEDLINE
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