scholarly journals Community Metabolic Interactions, Vitamin Production and Prebiotic Potential of Medicinal Herbs Used for Immunomodulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Christine T. Peterson ◽  
Stanislav N. Iablokov ◽  
Sasha Uchitel ◽  
Deepak Chopra ◽  
Josue Perez-Santiago ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Function ◽  
Immune Cell ◽  
Health Benefits ◽  
Cell Types ◽  
Short Chain Fatty Acids ◽  
Medicinal Herbs ◽  
Vitamin Production

Historically, the health benefits and immunomodulatory potential of medicinal herbs have been considered an intrinsic quality of the herb itself. We have hypothesized that the health benefits of medicinal herbs may be partially due to their prebiotic potential that alter gut microbiota leading to changes in short chain fatty acids and vitamin production or biotransformation of herb encoded molecules and secondary metabolites. Accumulating studies emphasize the relationship between the gut microbiota and host immune function. While largely unknown, these interactions are mediated by secreted microbial products that activate or repress a variety of immune cell types. Here we evaluated the effect of immunomodulatory, medicinal Ayurvedic herbs on gut microbiota in vitro using 16S rRNA sequencing to assess changes in community composition and functional potential. All immunomodulatory herbs displayed substantial prebiotic potential, targeting unique taxonomic groups. Application of genome reconstruction and analysis of biosynthetic capacity of herb selected communities suggests that many of the 11 herbs tested altered the community metabolism as the result of differential glycan harvest and sugar utilization and secreted products including multiple vitamins, butyrate, and propionate that may impact host physiology and immune function. Taken together, these results provide a useful framework for the further evaluation of these immunomodulatory herbs in vivo to maintain immune homeostasis or achieve desired regulation of immune components in the context of disease.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Administration of cardiac mesenchymal cells modulates innate immunity in the acute phase of myocardial infarction in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yi Kang ◽  
Marjan Nasr ◽  
Yiru Guo ◽  
Shizuka Uchida ◽  
Tyler Weirick ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Innate Immunity ◽  
Mechanism Of Action ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Mesenchymal Cell ◽  
Cell Types

Abstract Although cardiac mesenchymal cell (CMC) therapy mitigates post-infarct cardiac dysfunction, the underlying mechanisms remain unidentified. It is acknowledged that donor cells are neither appreciably retained nor meaningfully contribute to tissue regeneration—suggesting a paracrine-mediated mechanism of action. As the immune system is inextricably linked to wound healing/remodeling in the ischemically injured heart, the reparative actions of CMCs may be attributed to their immunoregulatory properties. The current study evaluated the consequences of CMC administration on post myocardial infarction (MI) immune responses in vivo and paracrine-mediated immune cell function in vitro. CMC administration preferentially elicited the recruitment of cell types associated with innate immunity (e.g., monocytes/macrophages and neutrophils). CMC paracrine signaling assays revealed enhancement in innate immune cell chemoattraction, survival, and phagocytosis, and diminished pro-inflammatory immune cell activation; data that identifies and catalogues fundamental immunomodulatory properties of CMCs, which have broad implications regarding the mechanism of action of CMCs in cardiac repair.

scholarly journals Anti-Inflammatory Activities of Pentaherbs formula and Its Influence on Gut Microbiota in Allergic Asthma

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2776 ◽  
Author(s):  
Miranda Tsang ◽  
Sau-Wan Cheng ◽  
Jing Zhu ◽  
Karam Atli ◽  
Ben Chan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Allergic Asthma ◽  
Herbal Medicines ◽  
Oral Intake ◽  
Allergic Diseases ◽  
Short Chain Fatty Acids ◽  
Mice Model ◽  
Anti Inflammatory

Allergic asthma is a highly prevalent airway inflammatory disease, which involves the interaction between the immune system, environmental and genetic factors. Co-relation between allergic asthma and gut microbiota upon the change of diet have been widely reported, implicating that oral intake of alternative medicines possess a potential in the management of allergic asthma. Previous clinical, in vivo, and in vitro studies have shown that the Pentaherbs formula (PHF) comprising five traditional Chinese herbal medicines Lonicerae Flos, Menthae Herba, Phellodendri Cortex, Moutan Cortex, and Atractylodis Rhizoma possesses an anti-allergic and anti-inflammatory potential through suppressing various immune effector cells. In the present study, to further investigate the anti-inflammatory activities of PHF in allergic asthma, intragastrical administration of PHF was found to reduce airway hyperresponsiveness, airway wall remodeling and goblet cells hyperplasia in an ovalbumin (OVA)-induced allergic asthma mice model. PHF also significantly suppressed pulmonary eosinophilia and asthma-related cytokines IL-4 and IL-33 in bronchoalveolar lavage (BAL) fluid. In addition, PHF modulated the splenic regulatory T cells population, up-regulated regulatory interleukin (IL)-10 in serum, altered the microbial community structure and the short chain fatty acids content in the gut of the asthmatic mice. This study sheds light on the anti-inflammatory activities of PHF on allergic asthma. It also provides novel in vivo evidence that herbal medicines can ameliorate symptoms of allergic diseases may potentially prevent the development of subsequent atopic disorder such as allergic asthma through the influence of the gut microbiota.

Cell-specific and targeted delivery of RNA moieties

2020 ◽  
Author(s):  
Aditi Bhargava ◽  
Peter Ohara ◽  
Luc Jasmin
Keyword(s):  
Nucleic Acids ◽  
Targeted Delivery ◽  
Immune Cell ◽  
Neuronal Cell ◽  
Cell Types ◽  
Specific Cell ◽  
Chemically Modified ◽  
Covalently Linked

AbstractDelivery of therapeutic moieties to specific cell types, such as neurons remains a challenge. Genes present in neurons are also expressed in non-neuronal cell types such as glia where they mediate non-targeted related functions. Thus, non-specific targeting of these proteins/channels has numerous unwanted side effects, as is the case with current small molecules or drug therapies. Current methodologies that use nanoparticles, lipid-mediated uptake, or mannitol in conjunction with lipids to deliver double-stranded RNA (dsRNA) have yielded mixed and unreliable results. We used a neuroanatomical tracer (B subunit of Cholera Toxin (CTB)) that binds to the ganglioside receptors (GM1) expressed on cells, including primary sensory neurons to deliver encapsulated dsRNA. This approach greatly improved delivery of dsRNA to the desired cells by enhancing uptake, reducing vehicle-mediated toxicity and protecting nucleotides from degradation by endonucleases. The delivery complex is internalized, and once inside the cell, the dsRNA naturally dissociates itself from the carrier complex and is very effective in knocking down cognate targets, both in vivo and in vitro. Past methods have used CTB-fusion proteins or chemically modified oligos or DNA moieties that have been covalently conjugated to CTB. Furthermore, CTB conjugated to an antigen, protein, or chemically modified nucleic acid is a potent activator of immune cell (T and B cells, macrophages) response, whereas CTB admixed with antigens or unmodified nucleic acids does not evoke this immune response. Importantly, in our method, the nucleic acids are not covalently linked to the carrier molecules. Thus, our method holds strong potential for targeted delivery of therapeutic moieties for cell types expressing GM1 receptors, including neuronal cell types.

scholarly journals Effects of IL8 and immune cells on the regulation of luteal progesterone secretion

Reproduction ◽  
2014 ◽  
Vol 148 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Heather Talbott ◽  
Abigail Delaney ◽  
Pan Zhang ◽  
Yangsheng Yu ◽  
Robert A Cushman ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Immune Cell ◽  
Neutrophil Migration ◽  
Prostaglandin F2α ◽  
Cell Types ◽  
Luteal Cell ◽  
Fibroblast Cells ◽  
Progesterone Synthesis

Recent studies have suggested that chemokines may mediate the luteolytic action of prostaglandin F2α (PGF). Our objective was to identify chemokines induced by PGFin vivoand to determine the effects of interleukin 8 (IL8) on specific luteal cell typesin vitro. Mid-cycle cows were injected with saline or PGF, ovaries were removed after 0.5–4 h, and expression of chemokine was analyzed by qPCR.In vitroexpression of IL8 was analyzed after PGF administration and with cell signaling inhibitors to determine the mechanism of PGF-induced chemokine expression. Purified neutrophils were analyzed for migration and activation in response to IL8 and PGF. Purified luteal cell types (steroidogenic, endothelial, and fibroblast cells) were used to identify which cells respond to chemokines. Neutrophils and peripheral blood mononuclear cells (PBMCs) were cocultured with steroidogenic cells to determine their effect on progesterone production.IL8,CXCL2,CCL2, andCCL8transcripts were rapidly increased following PGF treatmentin vivo. The stimulatory action of PGF onIL8mRNA expressionin vitrowas prevented by inhibition of p38 and JNK signaling. IL8, but not PGF, TNF, or TGFB1, stimulated neutrophil migration. IL8 had no apparent action in purified luteal steroidogenic, endothelial, or fibroblast cells, but stimulated ERK phosphorylation in neutrophils. In coculture experiments neither IL8 nor activated neutrophils altered basal or LH-stimulated luteal cell progesterone synthesis. In contrast, activated PBMCs inhibited LH-stimulated progesterone synthesis from cultured luteal cells. These data implicate a complex cascade of events during luteolysis, involving chemokine signaling, neutrophil recruitment, and immune cell action within the corpus luteum.

scholarly journals Seaweed Components as Potential Modulators of the Gut Microbiota

Marine Drugs ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. 358
Author(s):  
Emer Shannon ◽  
Michael Conlon ◽  
Maria Hayes
Keyword(s):  
Gut Microbiota ◽  
Large Scale ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Short Chain Fatty Acids ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Oral Bioaccessibility

Macroalgae, or seaweeds, are a rich source of components which may exert beneficial effects on the mammalian gut microbiota through the enhancement of bacterial diversity and abundance. An imbalance of gut bacteria has been linked to the development of disorders such as inflammatory bowel disease, immunodeficiency, hypertension, type-2-diabetes, obesity, and cancer. This review outlines current knowledge from in vitro and in vivo studies concerning the potential therapeutic application of seaweed-derived polysaccharides, polyphenols and peptides to modulate the gut microbiota through diet. Polysaccharides such as fucoidan, laminarin, alginate, ulvan and porphyran are unique to seaweeds. Several studies have shown their potential to act as prebiotics and to positively modulate the gut microbiota. Prebiotics enhance bacterial populations and often their production of short chain fatty acids, which are the energy source for gastrointestinal epithelial cells, provide protection against pathogens, influence immunomodulation, and induce apoptosis of colon cancer cells. The oral bioaccessibility and bioavailability of seaweed components is also discussed, including the advantages and limitations of static and dynamic in vitro gastrointestinal models versus ex vivo and in vivo methods. Seaweed bioactives show potential for use in prevention and, in some instances, treatment of human disease. However, it is also necessary to confirm these potential, therapeutic effects in large-scale clinical trials. Where possible, we have cited information concerning these trials.

scholarly journals Fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Lizhong Sun ◽  
Libang He ◽  
Wei Wu ◽  
Li Luo ◽  
Mingyue Han ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Immune Cell ◽  
Early Stage ◽  
Specific Treatment ◽  
Cell Types ◽  
Loss Of Function ◽  
Tissue Repair And Regeneration ◽  
Inflammatory Conditions

AbstractUnrestrained inflammation is harmful to tissue repair and regeneration. Immune cell membrane-camouflaged nanoparticles have been proven to show promise as inflammation targets and multitargeted inflammation controls in the treatment of severe inflammation. Prevention and early intervention of inflammation can reduce the risk of irreversible tissue damage and loss of function, but no cell membrane-camouflaged nanotechnology has been reported to achieve stage-specific treatment in these conditions. In this study, we investigated the prophylactic and therapeutic efficacy of fibroblast membrane-camouflaged nanoparticles for topical treatment of early inflammation (early pulpitis as the model) with the help of in-depth bioinformatics and molecular biology investigations in vitro and in vivo. Nanoparticles have been proven to act as sentinels to detect and competitively neutralize invasive Escherichia coli lipopolysaccharide (E. coli LPS) with resident fibroblasts to effectively inhibit the activation of intricate signaling pathways. Moreover, nanoparticles can alleviate the secretion of multiple inflammatory cytokines to achieve multitargeted anti-inflammatory effects, attenuating inflammatory conditions in the early stage. Our work verified the feasibility of fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage, which widens the potential cell types for inflammation regulation.

scholarly journals Effects of in vitro metabolism of a broccoli leachate, glucosinolates and S-methylcysteine sulphoxide on the human faecal microbiome

2020 ◽  
Author(s):  
Lee Kellingray ◽  
Gwénaëlle Le Gall ◽  
Joanne F. Doleman ◽  
Arjan Narbad ◽  
Richard F. Mithen
Keyword(s):  
Health Benefits ◽  
Short Chain Fatty Acids ◽  
Bacterial Isolates ◽  
Important Food ◽  
Human Gut ◽  
Important Food Source ◽  
And Function ◽  
Faecal Microbiome

Abstract Purpose Brassica are an important food source worldwide and are characterised by the presence of compounds called glucosinolates. Studies indicate that the glucosinolate derived bioactive metabolite sulphoraphane can elicit chemoprotective benefits on human cells. Glucosinolates can be metabolised in vivo by members of the human gut microbiome, although the prevalence of this activity is unclear. Brassica and Allium plants also contain S-methylcysteine sulphoxide (SMCSO), that may provide additional health benefits but its metabolism by gut bacteria is not fully understood. Methods We examined the effects of a broccoli leachate (BL) on the composition and function of human faecal microbiomes of five different participants under in vitro conditions. Bacterial isolates from these communities were then tested for their ability to metabolise glucosinolates and SMCSO. Results Microbial communities cultured in vitro in BL media were observed to have enhanced growth of lactic acid bacteria, such as lactobacilli, with a corresponding increase in the levels of lactate and short-chain fatty acids. Members of Escherichia isolated from these faecal communities were found to bioconvert glucosinolates and SMCSO to their reduced analogues. Conclusion This study uses a broccoli leachate to investigate the bacterial-mediated bioconversion of glucosinolates and SMCSO, which may lead to further products with additional health benefits to the host. We believe that this is the first study that shows the reduction of the dietary compound S-methylcysteine sulphoxide by bacteria isolated from human faeces.

scholarly journals Establishment of a Patient-Derived, Magnetic Levitation-Based, 3D Spheroid Granuloma Model for Human Tuberculosis.

2021 ◽  
Author(s):  
Leigh Ann Kotze ◽  
Caroline G.G. Beltran ◽  
Dirk Lang ◽  
Andre G Loxton ◽  
Susan Cooper ◽  
...  
Keyword(s):  
Immune Cell ◽  
Magnetic Levitation ◽  
Cell Types ◽  
Host Cells ◽  
Cellular Interactions ◽  
Cell Recruitment ◽  
Metabolic Heterogeneity ◽  
Histological Architecture

Tuberculous granulomas that develop in response to Mycobacterium tuberculosis (M.tb) infection are highly dynamic entities shaped by the host immune response and disease kinetics. Within this microenvironment, immune cell recruitment, polarization and activation is driven not only by co-existing cell types and multi-cellular interactions, but also by M.tb-mediated changes involving metabolic heterogeneity, epigenetic reprogramming and rewiring of the transcriptional landscape of host cells. There is an increased appreciation of the in vivo complexity, versatility and heterogeneity of the cellular compartment that constitutes the tuberculosis (TB) granuloma, and the difficulty in translating findings from animal models to human disease. Here we describe a novel biomimetic in vitro 3-dimentional (3D) human lung granuloma model, resembling early innate and adaptive stages of the TB granuloma spectrum, and present results of histological architecture, host transcriptional characterization, mycobacteriological features, cytokine profiles and spatial distribution of key immune cells. A range of manipulations of immune cell populations in these granulomas will allow the study of host/pathogen pathways involved in the outcome of infection, as well as pharmacological interventions.

scholarly journals Division of labor in honey bee gut microbiota for plant polysaccharide digestion

2019 ◽  
Vol 116 (51) ◽  
pp. 25909-25916 ◽  
Author(s):  
Hao Zheng ◽  
Julie Perreau ◽  
J. Elijah Powell ◽  
Benfeng Han ◽  
Zijing Zhang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Honey Bee ◽  
Short Chain Fatty Acids ◽  
Gene Expressions ◽  
Plant Polysaccharide ◽  
Genes Encoding ◽  
Host Nutrition ◽  
Different Strains

Bees acquire carbohydrates from nectar and lipids; and amino acids from pollen, which also contains polysaccharides including cellulose, hemicellulose, and pectin. These potential energy sources could be degraded and fermented through microbial enzymatic activity, resulting in short chain fatty acids available to hosts. However, the contributions of individual microbiota members to polysaccharide digestion have remained unclear. Through analysis of bacterial isolate genomes and a metagenome of the honey bee gut microbiota, we identify thatBifidobacteriumandGilliamellaare the principal degraders of hemicellulose and pectin. BothBifidobacteriumandGilliamellashow extensive strain-level diversity in gene repertoires linked to polysaccharide digestion. Strains from honey bees possess more such genes than strains from bumble bees. InBifidobacterium, genes encoding carbohydrate-active enzymes are colocated within loci devoted to polysaccharide utilization, as inBacteroidesfrom the human gut. Carbohydrate-active enzyme-encoding gene expressions are up-regulated in response to particular hemicelluloses both in vitro and in vivo. Metabolomic analyses document that bees experimentally colonized by different strains generate distinctive gut metabolomic profiles, with enrichment for specific monosaccharides, corresponding to predictions from genomic data. The other 3 core gut species clusters (Snodgrassellaand 2Lactobacillusclusters) possess few or no genes for polysaccharide digestion. Together, these findings indicate that strain composition within individual hosts determines the metabolic capabilities and potentially affects host nutrition. Furthermore, the niche specialization revealed by our study may promote overall community stability in the gut microbiomes of bees.

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