Publications by authors named "Ioana Marin"

6 Publications

  • Page 1 of 1

Experimental autoimmune encephalomyelitis is associated with changes of the microbiota composition in the gastrointestinal tract.

Sci Rep 2020 09 16;10(1):15183. Epub 2020 Sep 16.

Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA, 22908, USA.

The gut microbiome is known to be sensitive to changes in the immune system, especially during autoimmune diseases such as Multiple Sclerosis (MS). Our study examines the changes to the gut microbiome that occur during experimental autoimmune encephalomyelitis (EAE), an animal model for MS. We collected fecal samples at key stages of EAE progression and quantified microbial abundances with 16S V3-V4 amplicon sequencing. Our analysis of the data suggests that the abundance of commensal Lactobacillaceae decreases during EAE while other commensal populations belonging to the Clostridiaceae, Ruminococcaceae, and Peptostreptococcaceae families expand. Community analysis with microbial co-occurrence networks points to these three expanding taxa as potential mediators of gut microbiome dysbiosis. We also employed PICRUSt2 to impute MetaCyc Enzyme Consortium (EC) pathway abundances from the original microbial abundance data. From this analysis, we found that a number of imputed EC pathways responsible for the production of immunomodulatory compounds appear to be enriched in mice undergoing EAE. Our analysis and interpretation of results provides a detailed picture of the changes to the gut microbiome that are occurring throughout the course of EAE disease progression and helps to evaluate EAE as a viable model for gut dysbiosis in MS patients.
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http://dx.doi.org/10.1038/s41598-020-72197-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494894PMC
September 2020

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.

J Exp Med 2018 06 11;215(6):1627-1647. Epub 2018 Apr 11.

Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA

Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.
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http://dx.doi.org/10.1084/jem.20180247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987928PMC
June 2018

Microbiota alteration is associated with the development of stress-induced despair behavior.

Sci Rep 2017 03 7;7:43859. Epub 2017 Mar 7.

Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA, 22904, USA.

Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress.
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http://dx.doi.org/10.1038/srep43859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339726PMC
March 2017

Central Nervous System: (Immunological) Ivory Tower or Not?

Neuropsychopharmacology 2017 01 11;42(1):28-35. Epub 2016 Jul 11.

Center for Brain Immunology and Glia (BIG), Department of Neuroscience, Neuroscience Graduate Program, School of Medicine, University of Virginia, Charlottesville, VA, USA.

The view of the nervous system being the victim of destructive inflammation during autoimmunity, degeneration, or injury has been rapidly changing. Recent studies are supporting the idea that the immune system provides support for the nervous system at various levels. Though cell patrolling through the nervous system parenchyma is limited compared with other tissues, immune cell presence within the central nervous system (CNS; microglia), as well as around it (in the meningeal spaces and choroid plexus) has been shown to be important for brain tissue maintenance and function. This review primarily explores recent findings concerning neuroimmune interactions and their mechanisms under homeostatic conditions.
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http://dx.doi.org/10.1038/npp.2016.122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143482PMC
January 2017

Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli.

Immunity 2015 Apr;42(4):679-91

Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA. Electronic address:

Mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2, are the predominant cause of Rett syndrome, a disease characterized by both neurological symptoms and systemic abnormalities. Microglial dysfunction is thought to contribute to disease pathogenesis, and here we found microglia become activated and subsequently lost with disease progression in Mecp2-null mice. Mecp2 was found to be expressed in peripheral macrophage and monocyte populations, several of which also became depleted in Mecp2-null mice. RNA-seq revealed increased expression of glucocorticoid- and hypoxia-induced transcripts in Mecp2-deficient microglia and peritoneal macrophages. Furthermore, Mecp2 was found to regulate inflammatory gene transcription in response to TNF stimulation. Postnatal re-expression of Mecp2 using Cx3cr1(creER) increased the lifespan of otherwise Mecp2-null mice. These data suggest that Mecp2 regulates microglia and macrophage responsiveness to environmental stimuli to promote homeostasis. Dysfunction of tissue-resident macrophages might contribute to the systemic pathologies observed in Rett syndrome.
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http://dx.doi.org/10.1016/j.immuni.2015.03.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407145PMC
April 2015

Learning and memory ... and the immune system.

Learn Mem 2013 Sep 19;20(10):601-6. Epub 2013 Sep 19.

Center for Brain Immunology and Glia (BIG), Department of Neuroscience, Neuroscience Graduate Program, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.

The nervous system and the immune system are two main regulators of homeostasis in the body. Communication between them ensures normal functioning of the organism. Immune cells and molecules are required for sculpting the circuitry and determining the activity of the nervous system. Within the parenchyma of the central nervous system (CNS), microglia constantly monitor synapses and participate in their pruning during development and possibly also throughout life. Classical inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF), are released during neuronal activity and play a crucial role in regulating the strength of synaptic transmission. Systemically, proper functioning of the immune system is critical for maintaining normal nervous system function. Disruption of the immune system functioning leads to impairments in cognition and in neurogenesis. In this review we provide examples of the communication between the nervous and the immune systems in the interest of normal CNS development and function.
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http://dx.doi.org/10.1101/lm.028357.112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3768198PMC
September 2013