“…In being reactive to Stx2, MG cells could play a pivotal role in inflammatory mechanisms underlying cellular damage associated with neurological dysfunctions. In fact, previous work has demonstrated the role of MG cells in system homeostasis through a physiological balance of pro-inflammatory and antiinflammatory profiles (Sirerol-Piquer et al, 2019); thus, a shift toward a pro-inflammatory profile correlates with physiological and system damage. Under the present acute experimental conditions, toxin incubation triggered a pro-inflammatory profile in terms of IL1β and IFNγ synthesis and release, with a sharper effect when the catalytic subunit was present.…”
Shiga toxin (Stx) produced by enterohemorrhagic E. coli produces hemolytic uremic syndrome and encephalopathies in patients, which can lead to either reversible or permanent neurological abnormalities, or even fatal cases depending on the degree of intoxication. It has been observed that the inflammatory component plays a decisive role in the severity of the disease. Therefore, the objective of this work was to evaluate the behavior of microglial cell primary cultures upon Stx2 exposure and heat shock or lipopolysaccharide challenges, as cues which modulate cellular environments, mimicking fever and inflammation states, respectively. In these contexts, activated microglial cells incorporated Stx2, increased their metabolism, phagocytic capacity, and pro-inflammatory profile. Stx2 uptake was associated to receptor globotriaosylceramide (Gb3)-pathway. Gb3 had three clearly distinguishable distribution patterns which varied according to different contexts. In addition, toxin uptake exhibited both a Gb3-dependent and a Gb3-independent binding depending on those contexts. Altogether, these results suggest a fundamental role for microglial cells in pro-inflammatory processes in encephalopathies due to Stx2 intoxication and highlight the impact of environmental cues.
“…In being reactive to Stx2, MG cells could play a pivotal role in inflammatory mechanisms underlying cellular damage associated with neurological dysfunctions. In fact, previous work has demonstrated the role of MG cells in system homeostasis through a physiological balance of pro-inflammatory and antiinflammatory profiles (Sirerol-Piquer et al, 2019); thus, a shift toward a pro-inflammatory profile correlates with physiological and system damage. Under the present acute experimental conditions, toxin incubation triggered a pro-inflammatory profile in terms of IL1β and IFNγ synthesis and release, with a sharper effect when the catalytic subunit was present.…”
Shiga toxin (Stx) produced by enterohemorrhagic E. coli produces hemolytic uremic syndrome and encephalopathies in patients, which can lead to either reversible or permanent neurological abnormalities, or even fatal cases depending on the degree of intoxication. It has been observed that the inflammatory component plays a decisive role in the severity of the disease. Therefore, the objective of this work was to evaluate the behavior of microglial cell primary cultures upon Stx2 exposure and heat shock or lipopolysaccharide challenges, as cues which modulate cellular environments, mimicking fever and inflammation states, respectively. In these contexts, activated microglial cells incorporated Stx2, increased their metabolism, phagocytic capacity, and pro-inflammatory profile. Stx2 uptake was associated to receptor globotriaosylceramide (Gb3)-pathway. Gb3 had three clearly distinguishable distribution patterns which varied according to different contexts. In addition, toxin uptake exhibited both a Gb3-dependent and a Gb3-independent binding depending on those contexts. Altogether, these results suggest a fundamental role for microglial cells in pro-inflammatory processes in encephalopathies due to Stx2 intoxication and highlight the impact of environmental cues.
“…NSCs and adult neurogenesis are heavily influenced by the neighbouring niche cells, including microglia -the primary immune cells of the CNS [54]. The cytokines secreted by microglia have profound influence on adult neurogenesis [55], and since TAM signaling within immune cells is antiinflammatory [13,14,22], their role in microglia was tested.…”
Tyro3, Axl and Mertk are members of the TAM family of tyrosine kinase receptors. TAMs are activated by two structurally homologous ligands GAS6 and PROS1. TAM receptors and ligands are widely distributed and often co-expressed in the same cells allowing diverse functions across many systems including the immune, reproductive, vascular, and the developing and adult nervous systems. This review will focus specifically on TAM signaling in the nervous system, highlighting the essential roles they play in maintaining cell survival and homeostasis, cellular functions such as phagocytosis, immunity and tissue repair. Dysfunctional TAM signaling can cause complications in development, disruptions in homeostasis which can rouse autoimmunity, neuroinflammation and neurodegeneration. The development of therapeutics modulating TAM activities in the nervous system has great prospects, however, foremost we need a complete understanding of TAM signaling pathways.
“…An increasing amount of evidence shows that a continuous dialogue exists between microglia and NSCs, and that microglia play essential roles in the genesis of new neurons or glial cells during fetal brain development, but also in the adult brain [ 113 , 114 ]. The morphology and antigenicity of microglia in the adult brain is different in the stem cell reservoir zones from the other areas of the brain: they have a larger cell body, fewer and thicker processes, and lower expression of activated microglia markers, such as TREM2 and CD68 [ 113 , 115 , 116 ].…”
Section: “The Floor” For the Mc-stem Cell Tangomentioning
Macrophages (MCs) are present in all tissues, not only supporting homeostasis, but also playing an important role in organogenesis, post-injury regeneration, and diseases. They are a heterogeneous cell population due to their origin, tissue specificity, and polarization in response to aggression factors, depending on environmental cues. Thus, as pro-inflammatory M1 phagocytic MCs, they contribute to tissue damage and even fibrosis, but the anti-inflammatory M2 phenotype participates in repairing processes and wound healing through a molecular interplay with most cells in adult stem cell niches. In this review, we emphasize MC phenotypic heterogeneity in health and disease, highlighting their systemic and systematic contribution to tissue homeostasis and repair. Unraveling the intervention of both resident and migrated MCs on the behavior of stem cells and the regulation of the stem cell niche is crucial for opening new perspectives for novel therapeutic strategies in different diseases.
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