<i>Brucella abortus</i>‐activated microglia induce neuronal death through primary phagocytosis

Rodrı́guez, Ana; Delpino, M. Victoria; Miraglia, María Cruz; Franco, Miriam M. Costa; Barrionuevo, Paula; Dennis, Vida A.; Oliveira, Sérgio C.; Giambartolomei, Guillermo H.

doi:10.1002/glia.23149

Cited by 32 publications

(37 citation statements)

References 56 publications

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“…Moreover, excessively activated microglia have detrimental effects on neurogenesis, contribute to neuronal death and aggravate long‐term neurological deficits by hindering axonal regeneration (Kitayama, Ueno, Itakura, & Yamashita, ; Papageorgiou et al, ; Rodriguez et al, ). In vivo, microglia may even have a functional interaction with peripherally derived immune cells in the circulation in healthy subjects (Kanegawa et al, ).…”

Section: The Role Of Microglia In Neurological Diseases: Friend or Foe?mentioning

confidence: 99%

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Han

Zhu

Zhang

et al. 2018

Glia

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Microglia are prominent immune cells in the central nervous system (CNS) and are critical players in both neurological development and homeostasis, and in neurological diseases when dysfunctional. Our previous understanding of the phenotypes and functions of microglia has been greatly extended by a dearth of recent investigations. Distinct genetically defined subsets of microglia are now recognized to perform their own independent functions in specific conditions. The molecular profiling of single microglial cells indicates extensively heterogeneous reactions in different neurological disorders, resulting in multiple potentials for crosstalk with other kinds of CNS cells such as astrocytes and neurons. In settings of neurological diseases it could thus be prudent to establish effective cell‐based therapies by targeting entire microglial networks. Notably, activated microglial depletion through genetic targeting or pharmacological therapies within a suitable time window can stimulate replenishment of the CNS niche with new microglia. Additionally, enforced repopulation through provision of replacement cells also represents a potential means of exchanging dysfunctional with functional microglia. In each setting the newly repopulated microglia might have the potential to resolve ongoing neuroinflammation. In this review, we aim to summarize the most recent knowledge of microglia and to highlight microglial depletion and subsequent repopulation as a promising cell replacement therapy. Although glial cell replacement therapy is still in its infancy and future translational studies are still required, the approach is scientifically sound and provides new optimism for managing the neurotoxicity and neuroinflammation induced by activated microglia.

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Section: The Role Of Microglia In Neurological Diseases: Friend or Foe?mentioning

confidence: 99%

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Han

Zhu

Zhang

et al. 2018

Glia

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“…Brucellosis is becoming a worldwide epidemic within a certain scope (Zhong et al, 2016). Brucella not only has the ability to resist phagocytosis, but can also prevent antigen-specific cell recognition (Rodríguez et al, 2017). This ability contributes to Brucella survival and reproduction and can often lead to a chronic infection.…”

Section: Discussionmentioning

confidence: 99%

Effects of JAK2 / STAT3 Signaling Pathway Activation on Intracellular Survival of Brucella

Yi¹

2018

PVJ

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Brucellosis is an important zoonotic pathogen of worldwide distribution that causes disease in both humans and animals. Brucella can weaken the immune ability of host cells and its pathogenesis depends on its ability to replicate intracellularly and inhibit host cell apoptosis. The JAK2/STAT3 pathway is known to regulate various biological functions, to include cell differentiation, cell death, and apoptosis. However, the role of this pathway in the survival of virulent or low virulent Brucella strains in macrophages remains largely uncharacterized. In this study, the JAK2/STAT3 pathway was found to be activated by both smooth Brucella abortus 2308 (B. abortus; virulent) and rough B. abortus RB51 (low virulent), but only B. abortus RB51 significantly induced JAK2 and STAT3 phosphorylation in a timedependent manner. Furthermore, in B. abortus RB51, JAK2/STAT3 phosphorylation was inhibited by AG490 (inhibitor of JAK2/STAT3 pathway) in a dosedependent manner and B. abortus RB51-mediated apoptosis and cytokines (IL-6, TNF-α) expression were also inhibited. These findings suggest that JAK2/ STAT3 pathway is important to intercellular survival during a B. abortus RB51 infection, but does not appear to play an apparent role in B. abortus 2308 survival. , 2018. Effects of JAK2 / STAT3 Signaling Pathway Activation on Intracellular Survival of Brucella. Pak Vet J, 38(2): 153-158. http://dx.

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“…In addition, we have described that activation of glial cells by B. abortus is crucial in neurobrucellosis pathology [ 6 ]. B. abortus -activated astrocytes and microglia secrete pro-inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, C-C motif chemokine ligand 2 CCL-2, C-X-C motif chemokine ligand 1 (CXCL1), metalloproteinase (MMP)-9, and nitric oxide (NO), among others [ 6 , 7 , 8 ]. These inflammatory mediators, and astrocytes/microglia-secreted IL-1β in particular, activate the BBB, allowing monocyte and neutrophil transmigration [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Brucella abortus-Stimulated Platelets Activate Brain Microvascular Endothelial Cells Increasing Cell Transmigration through the Erk1/2 Pathway

et al. 2020

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Central nervous system invasion by bacteria of the genus Brucella results in an inflammatory disorder called neurobrucellosis. A common feature associated with this pathology is blood–brain barrier (BBB) activation. However, the underlying mechanisms involved with such BBB activation remain unknown. The aim of this work was to investigate the role of Brucella abortus-stimulated platelets on human brain microvascular endothelial cell (HBMEC) activation. Platelets enhanced HBMEC activation in response to B. abortus infection. Furthermore, supernatants from B. abortus-stimulated platelets also activated brain endothelial cells, inducing increased secretion of IL-6, IL-8, CCL-2 as well as ICAM-1 and CD40 upregulation on HBMEC compared with supernatants from unstimulated platelets. Outer membrane protein 19, a B. abortus lipoprotein, recapitulated B. abortus-mediated activation of HBMECs by platelets. In addition, supernatants from B. abortus-activated platelets promoted transendothelial migration of neutrophils and monocytes. Finally, using a pharmacological inhibitor, we demonstrated that the Erk1/2 pathway is involved in the endothelial activation induced by B. abortus-stimulated platelets and also in transendothelial migration of neutrophils. These results describe a mechanism whereby B. abortus-stimulated platelets induce endothelial cell activation, promoting neutrophils and monocytes to traverse the BBB probably contributing to the inflammatory pathology of neurobrucellosis.

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Brucella abortus‐activated microglia induce neuronal death through primary phagocytosis

Cited by 32 publications

References 56 publications

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

Effects of JAK2 / STAT3 Signaling Pathway Activation on Intracellular Survival of Brucella

Brucella abortus-Stimulated Platelets Activate Brain Microvascular Endothelial Cells Increasing Cell Transmigration through the Erk1/2 Pathway

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