Potential Role of Gut Microbiota in Induction and Regulation of Innate Immune Memory

The Role of Cell Metabolism in Innate Immune Memory

Journal of Innate Immunity ◽

10.1159/000512280 ◽

2020 ◽

pp. 1-9

Author(s):

Anaisa Valido Ferreira ◽

Jorge Domiguéz-Andrés ◽

Mihai Gheorghe Netea

Keyword(s):

Metabolic Pathways ◽

Tricarboxylic Acid Cycle ◽

Cell Metabolism ◽

Innate Immune ◽

Immune Memory ◽

Functional Changes ◽

Trained Immunity ◽

Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

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Gut microbiota influence in type 2 diabetes mellitus (T2DM)

Gut Pathogens ◽

10.1186/s13099-021-00446-0 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

A. L. Cunningham ◽

J. W. Stephens ◽

D. A. Harris

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Gut Microbiota ◽

Potential Role ◽

Evidence Base ◽

Human Metabolism ◽

Altered Glucose

AbstractA strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.

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The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

International Journal of Molecular Sciences ◽

10.3390/ijms22052578 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2578

Author(s):

Trim Lajqi ◽

Christian Marx ◽

Hannes Hudalla ◽

Fabienne Haas ◽

Silke Große ◽

...

Keyword(s):

Oxygen Consumption ◽

Immune Tolerance ◽

Immune Cells ◽

Low Dose ◽

Innate Immune ◽

Immune Memory ◽

Innate Immune Cells ◽

Atp Production ◽

Dose Dependent

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.

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Houttuynia cordatamodulates oral innate immune mediators: potential role of herbal plant on oral health

Oral Diseases ◽

10.1111/odi.12313 ◽

2015 ◽

Vol 21 (4) ◽

pp. 512-518 ◽

Cited By ~ 7

Author(s):

S Satthakarn ◽

WO Chung ◽

A Promsong ◽

W Nittayananta

Keyword(s):

Oral Health ◽

Potential Role ◽

Innate Immune ◽

Immune Mediators ◽

Herbal Plant

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The potential role of gut microbiota in pancreatic disease: A systematic review

Pancreatology ◽

10.1016/j.pan.2017.09.002 ◽

2017 ◽

Vol 17 (6) ◽

pp. 867-874 ◽

Cited By ~ 28

Author(s):

Robert Memba ◽

Sinead N. Duggan ◽

Hazel M. Ni Chonchubhair ◽

Oonagh M. Griffin ◽

Yasir Bashir ◽

...

Keyword(s):

Systematic Review ◽

Gut Microbiota ◽

Potential Role ◽

Pancreatic Disease

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Borrelia burgdorferi Resistance to a Major Skin Antimicrobial Peptide Is Independent of Outer Surface Lipoprotein Content

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00558-09 ◽

2009 ◽

Vol 53 (10) ◽

pp. 4490-4494 ◽

Cited By ~ 8

Author(s):

Amit Sarkar ◽

Kit Tilly ◽

Philip Stewart ◽

Aaron Bestor ◽

James M. Battisti ◽

...

Keyword(s):

Borrelia Burgdorferi ◽

Antimicrobial Peptide ◽

Immune Evasion ◽

Essential Role ◽

Potential Role ◽

Innate Immune ◽

Initial Stage ◽

Mammalian Infection ◽

Innate Immune Evasion

ABSTRACT We hypothesize a potential role for Borrelia burgdorferi OspC in innate immune evasion at the initial stage of mammalian infection. We demonstrate that B. burgdorferi is resistant to high levels (>200 μg/ml) of cathelicidin and that this antimicrobial peptide exhibits limited binding to the spirochetal outer membrane, irrespective of OspC or other abundant surface lipoproteins. We conclude that the essential role of OspC is unrelated to resistance to this component of innate immunity.

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Potential Role of Gut Microbiota in ALS Pathogenesis and Possible Novel Therapeutic Strategies

Journal of Clinical Gastroenterology ◽

10.1097/mcg.0000000000001042 ◽

2018 ◽

Vol 52 ◽

pp. S68-S70 ◽

Cited By ~ 16

Author(s):

Letizia Mazzini ◽

Luca Mogna ◽

Fabiola De Marchi ◽

Angela Amoruso ◽

Marco Pane ◽

...

Keyword(s):

Gut Microbiota ◽

Potential Role ◽

Therapeutic Strategies ◽

Novel Therapeutic Strategies ◽

Novel Therapeutic

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The application of omics techniques to understand the role of the gut microbiota in inflammatory bowel disease

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818822250 ◽

2019 ◽

Vol 12 ◽

pp. 175628481882225 ◽

Cited By ~ 14

Author(s):

Jonathan P. Segal ◽

Benjamin H. Mullish ◽

Mohammed Nabil Quraishi ◽

Animesh Acharjee ◽

Horace R. T. Williams ◽

...

Keyword(s):

Systems Biology ◽

Gut Microbiota ◽

Potential Role ◽

Intestinal Inflammation ◽

Clinical Care ◽

Complex Interaction ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Compositional Changes

The aetiopathogenesis of inflammatory bowel diseases (IBD) involves the complex interaction between a patient’s genetic predisposition, environment, gut microbiota and immune system. Currently, however, it is not known if the distinctive perturbations of the gut microbiota that appear to accompany both Crohn’s disease and ulcerative colitis are the cause of, or the result of, the intestinal inflammation that characterizes IBD. With the utilization of novel systems biology technologies, we can now begin to understand not only details about compositional changes in the gut microbiota in IBD, but increasingly also the alterations in microbiota function that accompany these. Technologies such as metagenomics, metataxomics, metatranscriptomics, metaproteomics and metabonomics are therefore allowing us a deeper understanding of the role of the microbiota in IBD. Furthermore, the integration of these systems biology technologies through advancing computational and statistical techniques are beginning to understand the microbiome interactions that both contribute to health and diseased states in IBD. This review aims to explore how such systems biology technologies are advancing our understanding of the gut microbiota, and their potential role in delineating the aetiology, development and clinical care of IBD.

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