Immune Regulatory Functions of Macrophages and Microglia in Central Nervous System Diseases

Poppell, Michael; Hammel, Grace; Ren, Yi

doi:10.3390/ijms24065925

Cited by 9 publications

(4 citation statements)

References 328 publications

(439 reference statements)

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“…It was reported that massive activation of microglia after rickettsial infection results in neurotoxicity and inflammation of the CNS, leading to the death of infected mice [12]. However, in the context of the published data, we suppose that microglia migrate to the site of neuronal damage and exert neuroprotective processes, as this is their authentic function in a diseased brain [39]. The recent review summarizes the pathogenesis of Rickettsia-infected mice and presents a set of upregulated genes coding for specific cytokines and indicates affected brain cells [14].…”

Section: Discussionmentioning

confidence: 76%

Rickettsia Deregulates Genes Coding for the Neurotoxic Cell Response Pathways in Cerebrocortical Neurons In Vitro

Cente

Danchenko

Škultéty

et al. 2023

Cells

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Rickettsial infections of the central nervous system (CNS) are manifested by severe neurological symptoms and represent a serious life-threatening condition. Despite the considerable health danger, only a few studies have been conducted focusing on the pathogenesis induced by Rickettsia sp. in CNS. To investigate the signaling pathways associated with the neurotoxic effects of rickettsiae, we employed an experimental model of cerebrocortical neurons combined with molecular profiling and comprehensive bioinformatic analysis. The cytopathic effect induced by Rickettsia akari and Rickettsia slovaca was demonstrated by decreased neuronal viability, structural changes in cell morphology, and extensive fragmentation of neurites in vitro. Targeted profiling revealed the deregulation of genes involved in the neuroinflammatory and neurotoxic cell response pathways. Although quantitative analysis showed differences in gene expression response, functional annotation revealed that the biological processes are largely shared between both Rickettsia species. The identified enriched pathways are associated with cytokine signaling, chemotaxis of immune cells, responses to infectious agents, interactions between neurons, endothelial and glial cells, and regulation of neuronal apoptotic processes. The findings of our study provide new insight into the etiopathogenesis of CNS infection and further expand the understanding of molecular signaling associated with neuroinvasive Rickettsia species.

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Section: Discussionmentioning

confidence: 76%

Rickettsia Deregulates Genes Coding for the Neurotoxic Cell Response Pathways in Cerebrocortical Neurons In Vitro

Cente

Danchenko

Škultéty

et al. 2023

Cells

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“…При РС в качестве механизма повреждения ЦНС предполагается аберрантная стимуляция плазматических и В-клеток, приводящая к выработке аутоантител против специфических антигенов миелина. В экспериментах было показано, что взаимодействие В-лимфоцитов с CD4 + -Т-клетками инициирует адаптивный иммунный ответ на антигены миелина, а подавление В-клеточного иммунитета приводит к снижению воспаления и выраженности клинических проявлений [22,23]. Я.А.…”

Section: таблица 1 показатели клеточного иммунитета у обследованных б...unclassified

Cell-Mediated Immunity in Multiple Sclerosis Patients Who Discontinued Therapy with an Integrin Inhibitor

Belova,

Chuksina,

Kotov

et al. 2024

Annals of Clinical and Experimental Neurology

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Introduction. Natalizumab (NTZ) is a humanized monoclonal antibody (mAb) that selectively inhibits α4-integrin adhesion molecule located on the surface of lymphocytes and prevents their trafficking into the central nervous system (CNS). The aim of this study was to identify characteristics of lymphocyte population and subpopulation pattern in the peripheral blood (PB) of multiple sclerosis (MS) patients who discontinued NTZ due to an increased risk of developing developing progressive multifocal leukoencephalopathy. Materials and methods. We conducted an open-label prospective observational study in 26 MS patients. Of those, 6 patients had rapidly progressive MS, 10 patients discontinued NTZ and had confirmed relapses afterwards, and 10 patients received NTZ and had no relapses during the washout period. Ten apparently healthy individuals were used as controls. Cell-mediated immunity parameters were evaluated by flow cytometry using a panel of mAbs to differentiation antigens of PB lymphocytes. Results. Patients who discontinued NTZ had significantly decreased absolute lymphocyte counts in PB, decreased T-cytotoxic, NKT and B1 lymphocyte subpopulation levels, and decreased activated T-cell (CD3+HLA–DR+) levels, which may be related to their redistribution, passing through the blood-brain barrier, and trafficking into the central nervous system. CD20+ В-cell levels did not differ from normal. Additional immune predictors of MS relapses after NTZ discontinuation can include decreased absolute count of PB lymphocytes and decreased percentage of CD3+CD8+ T-cell, NKT-cell, and B1-cell (CD19+CD5+) subpopulations. Significantly increased levels of CD25+- and CD38+-activated B-cells compared with the normal levels in naïve patients and subjects without relapses after NTZ discontinuation may suggest a high activation potential of the circulating B-cell pool and, therefore, a high risk of MS relapses. Conclusions. The changes in the lymphocyte subpopulation pattern in the PB of MS patients after NTZ discontinuation may have a prognostic value for assessing the risk of relapses; they justified switching patients to anti-B-cell therapy.

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“…These pathways culminate in the activation of astrocytes and microglia in the CNS and the release of a variety of pro-inflammatory molecules, including cytokines, chemokines, ROS, and nitric oxide, via peripheral pro-inflammatory mediators to promote a local immune response and lead to neuroinflammation ( Ransohoff and Brown, 2012 ). Activated microglia can promote immune cell maturation through antigen presentation, and the latter secrete cytokines to promote glial cell activation, creating positive feedback of the immune response ( Poppell et al, 2023 ). Glutamate-glutamine cycling and metabolic homeostasis can influence cell interactions, inflammatory signaling activation, modulation of cellular excitability, and cell survival ( Zhang et al, 2022 ).…”

Section: Mechanisms By Which Peripheral Inflammation Promotes Central...mentioning

confidence: 99%

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

Tan,

Chen,

Kong

et al. 2023

Front. Aging Neurosci.

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Cognitive impairments, such as learning and memory deficits, may occur in susceptible populations including the elderly and patients who are chronically ill or have experienced stressful events, including surgery, infection, and trauma. Accumulating lines of evidence suggested that peripheral inflammation featured by the recruitment of peripheral immune cells and the release of pro-inflammatory cytokines may be activated during aging and these conditions, participating in peripheral immune system-brain communication. Lots of progress has been achieved in deciphering the core bridging mechanism connecting peripheral inflammation and cognitive impairments, which may be helpful in developing early diagnosis, prognosis evaluation, and prevention methods based on peripheral blood circulation system sampling and intervention. In this review, we summarized the evolving evidence on the prevalence of peripheral inflammation-associated neurocognitive impairments and discussed the research advances in the underlying mechanisms. We also highlighted the prevention and treatment strategies against peripheral inflammation-associated cognitive dysfunction.

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Immune Regulatory Functions of Macrophages and Microglia in Central Nervous System Diseases

Cited by 9 publications

References 328 publications

Rickettsia Deregulates Genes Coding for the Neurotoxic Cell Response Pathways in Cerebrocortical Neurons In Vitro

Rickettsia Deregulates Genes Coding for the Neurotoxic Cell Response Pathways in Cerebrocortical Neurons In Vitro

Cell-Mediated Immunity in Multiple Sclerosis Patients Who Discontinued Therapy with an Integrin Inhibitor

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications

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