scholarly journals The Impact of IgA and the Microbiota on CNS Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Annie Pu ◽  
Dennis S. W. Lee ◽  
Baweleta Isho ◽  
Ikbel Naouar ◽  
Jennifer L. Gommerman
Keyword(s):  
Immune Cells ◽  
Preclinical Models ◽  
Potential Therapeutic Target ◽  
Cns Disease ◽  
Mechanistic Insight ◽  
Circulating Lymphocytes ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
The Impact ◽  
Insight Into

Although anatomically distant from the central nervous system (CNS), gut-derived signals can dynamically regulate both peripheral immune cells and CNS-resident glial cells to modulate disease. Recent discoveries of specific microbial taxa and microbial derived metabolites that modulate neuroinflammation and neurodegeneration have provided mechanistic insight into how the gut may modulate the CNS. Furthermore, the participation of the gut in regulation of peripheral and CNS immune activity introduces a potential therapeutic target. This review addresses emerging literature on how the microbiome can affect glia and circulating lymphocytes in preclinical models of human CNS disease. Critically, this review also discusses how the host may in turn influence the microbiome, and how this may impact CNS homeostasis and disease, potentially through the production of IgA.

scholarly journals Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Science ◽  
2019 ◽  
Vol 365 (6460) ◽  
pp. eaav7188 ◽  
Author(s):  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Expression Profiles ◽  
Human Microglia ◽  
Histocompatibility Complex ◽  
The Central Nervous System ◽  
Reference Map ◽  
Peripheral Immune Cells ◽  
Genomic Map ◽  
Cellular Components

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

scholarly journals What Guides Peripheral Immune Cells into the Central Nervous System?

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2041
Author(s):  
Theresa Greiner ◽  
Markus Kipp
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Cells ◽  
Progressive Disease ◽  
Demyelinating Disease ◽  
Disease Stage ◽  
Secondary Progressive ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Peripheral Immune Cells

Multiple sclerosis (MS), an immune-mediated demyelinating disease of the central nervous system (CNS), initially presents with a relapsing-remitting disease course. During this early stage of the disease, leukocytes cross the blood–brain barrier to drive the formation of focal demyelinating plaques. Disease-modifying agents that modulate or suppress the peripheral immune system provide a therapeutic benefit during relapsing-remitting MS (RRMS). The majority of individuals with RRMS ultimately enter a secondary progressive disease stage with a progressive accumulation of neurologic deficits. The cellular and molecular basis for this transition is unclear and the role of inflammation during the secondary progressive disease stage is a subject of intense and controversial debate. In this review article, we discuss the following main hypothesis: during both disease stages, peripheral immune cells are triggered by CNS-intrinsic stimuli to invade the brain parenchyma. Furthermore, we outline the different neuroanatomical routes by which peripheral immune cells might migrate from the periphery into the CNS.

Designing Relevant Preclinical Rodent Models for Studying Links Between Nutrition, Obesity, Metabolism, and Cancer

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Elaine M. Glenny ◽  
Michael F. Coleman ◽  
Erin D. Giles ◽  
Elizabeth A. Wellberg ◽  
Stephen D. Hursting
Keyword(s):  
Treatment Options ◽  
Annual Review ◽  
Publication Date ◽  
Rodent Models ◽  
Cancer Model ◽  
Preclinical Models ◽  
Cancer Models ◽  
The Impact ◽  
The Relationship ◽  
Insight Into

Diet and nutrition are intricately related to cancer prevention, growth, and treatment response. Preclinical rodent models are a cornerstone to biomedical research and remain instrumental in our understanding of the relationship between cancer and diet and in the development of effective therapeutics. However, the success rate of translating promising findings from the bench to the bedside is suboptimal. Well-designed rodent models will be crucial to improving the impact basic science has on clinical treatment options. This review discusses essential experimental factors to consider when designing a preclinical cancer model with an emphasis on incorporating these models into studies interrogating diet, nutrition, and metabolism. The aims of this review are to ( a) provide insight into relevant considerations when designing cancer models for obesity, nutrition, and metabolism research; ( b) identify common pitfalls when selecting a rodent model; and ( c) discuss strengths and limitations of available preclinical models. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Neuroimmune interactions and pain during postnatal development

2013 ◽  
pp. 65-73
Author(s):  
David Vega-Avelaira ◽  
Simon Beggs
Keyword(s):  
Postnatal Development ◽  
Immune Cells ◽  
Defensive Responses ◽  
Nociceptive Pathways ◽  
Neuroimmune Interactions ◽  
The Central Nervous System ◽  
And Function ◽  
Type Of Injury ◽  
The Impact ◽  
Role And Function

The immune system is essential for identifying and mounting defensive responses to tissue damage and infection. In addition, it is increasingly recognized that interactions between immune cells and nociceptive pathways can modulate pain sensitivity. The role and function of immune cells in the central nervous system changes during postnatal development, and as a result, the impact of neuroimmune interactions on pain signalling varies with both age and the type of injury.

scholarly journals CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages

2020 ◽  
Vol 117 (38) ◽  
pp. 23336-23338 ◽  
Author(s):  
Fengyang Lei ◽  
Naiwen Cui ◽  
Chengxin Zhou ◽  
James Chodosh ◽  
Demetrios G. Vavvas ◽  
...  
Keyword(s):  
Small Molecule ◽  
Immune Cells ◽  
Colony Stimulating Factor ◽  
Molecule Inhibitor ◽  
Long Term Changes ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
Stimulating Factor ◽  
Practical Implications

Colony-stimulating factor 1 receptor (CSF1R) inhibition has been proposed as a method for microglia depletion, with the assumption that it does not affect peripheral immune cells. Here, we show that CSF1R inhibition by PLX5622 indeed affects the myeloid and lymphoid compartments, causes long-term changes in bone marrow-derived macrophages by suppressing interleukin 1β, CD68, and phagocytosis but not CD208, following exposure to endotoxin, and also reduces the population of resident and interstitial macrophages of peritoneum, lung, and liver but not spleen. Thus, small-molecule CSF1R inhibition is not restricted to microglia, causing strong effects on circulating and tissue macrophages that perdure long after cessation of the treatment. Given that peripheral monocytes repopulate the central nervous system after CSF1R inhibition, these changes have practical implications for relevant experimental data.

scholarly journals Emerging Roles for Microglial Phagocytic Signaling in Epilepsy

2019 ◽  
Vol 20 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Season K. Wyatt-Johnson ◽  
Amy L. Brewster
Keyword(s):  
Central Nervous System ◽  
Immune Cells ◽  
Strong Support ◽  
Signaling Molecules ◽  
Preclinical Models ◽  
Synaptic Loss ◽  
The Central Nervous System ◽  
Spontaneous Recurrent Seizures ◽  
Models Of Epilepsy ◽  
Novel Therapeutic

Microglia are the resident immune cells and professional phagocytes of the central nervous system. However, little is known about the contribution of their phagocytic signaling to the neuropathology and pathophysiology of epilepsy. Here, we summarize and discuss the implications of recent evidence supporting that aberrant microglia phagocytic activity and alterations in phagocytosis signaling molecules occur in association with microglia–neuronal contacts, neuronal/synaptic loss, and spontaneous recurrent seizures in human and preclinical models of epilepsy. This body of evidence provides strong support that the microglial contribution to epileptogenic networks goes beyond inflammation, and suggests that phagocytic signaling molecules may be novel therapeutic targets for epilepsy.

scholarly journals Role of Peripheral Immune Cells in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Sci ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 12
Author(s):  
Sarah Dhaiban ◽  
Mena Al-Ani ◽  
Noha Mousaad Elemam ◽  
Mahmood H. Al-Aawad ◽  
Zeinab Al-Rawi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Cells ◽  
Autoimmune Encephalomyelitis ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Exact Etiology ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the myelination of the neurons present in the central nervous system (CNS). The exact etiology of MS development is unclear, but various environmental and genetic factors might play a role in initiating the disease. Experimental autoimmune encephalomyelitis (EAE) is a mouse model that is used to study the pathophysiology of MS disease as well as the effects of possible therapeutic agents. In addition, autoreactive immune cells trigger an inflammatory process upon the recognition of CNS antigens, which leads to destruction of the neurons. These include innate immune cells such as macrophages, dendritic cells, and natural killer cells. Additionally, the activation and extravasation of adaptive immune cells such as CD4+ T cells into the CNS may lead to further exacerbation of the disease. However, many studies revealed that immune cells could have either a protective or pathological role in MS. In this review, we highlight the roles of innate and adaptive immune cellular and soluble players that contribute to the pathogenesis of MS and EAE, which may be used as potential targets for therapy.

scholarly journals Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

2020 ◽  
Author(s):  
Bertrand Bryche ◽  
Audrey St Albin ◽  
Severine Murri ◽  
Sandra Lacôte ◽  
Coralie Pulido ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lamina Propria ◽  
Olfactory Epithelium ◽  
Immune Cells ◽  
Olfactory Neurons ◽  
Syrian Hamsters ◽  
Sustentacular Cells ◽  
The Central Nervous System ◽  
The Impact

AbstractAnosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-COV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria.

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