Innate immune memory of tissue‐resident macrophages and trained innate immunity: Re‐vamping vaccine concept and strategies

The regulation of innate immunity is substantially more ‘plastic’ than previously appreciated. Innate immune memory (manifested through trained immunity and tolerance) is a recently described epigenetic phenomenon that is a model example, with broad implications for infectious disease, allergy and autoimmunity. Training the innate immune system to combat infections and temper inappropriate responses in non-communicable diseases will likely be an area of intense research. Innate immunity is influenced by short chain fatty acids, which are the natural products of digestion by the intestinal microbiota that possess inherent histone deacetylase inhibitory properties. It therefore stands to reason that a healthy gut microbiome may well influence mucosal and systemic trained immunity via short chain fatty acids. There is a lack of data on this specific topic, and we discuss potential relationships based on available and preliminary evidence. Understanding the link between intestinal microbiome composition, capacity for short chain fatty acid production and downstream effects on innate immune memory in early life will have important implications for host immunobiology. In this review we explore the intersection between the gut microbiota, short chain fatty acids and epigenetic regulation of innate immunity with a focus on early life.

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Innate Immunity and Neuroinflammation in Neuropsychiatric Conditions Including Autism Spectrum Disorders: Role of Innate Immune Memory

Cytokines ◽

10.5772/intechopen.87167 ◽

2020 ◽

Author(s):

Harumi Jyonouchi

Keyword(s):

Innate Immunity ◽

Autism Spectrum Disorders ◽

Autism Spectrum ◽

Innate Immune ◽

Immune Memory ◽

Spectrum Disorders ◽

Neuropsychiatric Conditions

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A trade-off switch of two immunological memories in Caenorhabditis elegans reinfected by bacterial pathogens

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.013923 ◽

2020 ◽

Vol 295 (50) ◽

pp. 17323-17336

Author(s):

Jinyuan Yan ◽

Ninghui Zhao ◽

Zhongshan Yang ◽

Yuhong Li ◽

Hua Bai ◽

...

Keyword(s):

Innate Immunity ◽

Caenorhabditis Elegans ◽

Pathogenic Bacteria ◽

Immunological Memory ◽

Innate Immune ◽

Microbial Pathogens ◽

Immune Memory ◽

Microbial Infection ◽

Trade Off ◽

Chemosensory Neurons

Recent studies have suggested that innate immune responses exhibit characteristics associated with memory linked to modulations in both vertebrates and invertebrates. However, the diverse evolutionary paths taken, particularly within the invertebrate taxa, should lead to similarly diverse innate immunity memory processes. Our understanding of innate immune memory in invertebrates primarily comes from studies of the fruit fly Drosophila melanogaster, the generality of which is unclear. Caenorhabditis elegans typically inhabits soil harboring a variety of fatal microbial pathogens; for this invertebrate, the innate immune system and aversive behavior are the major defensive strategies against microbial infection. However, their characteristics of immunological memory remains infantile. Here we discovered an immunological memory that promoted avoidance and suppressed innate immunity during reinfection with bacteria, which we revealed to be specific to the previously exposed pathogens. During this trade-off switch of avoidance and innate immunity, the chemosensory neurons AWB and ADF modulated production of serotonin and dopamine, which in turn decreased expression of the innate immunity-associated genes and led to enhanced avoidance via the downstream insulin-like pathway. Therefore, our current study profiles the immune memories during C. elegans reinfected by pathogenic bacteria and further reveals that the chemosensory neurons, the neurotransmitter(s), and their associated molecular signaling pathways are responsible for a trade-off switch between the two immunological memories.

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Trained Immunity and Cardiometabolic Disease

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.120.314215 ◽

2020 ◽

Author(s):

Ioannis Mitroulis ◽

George Hajishengallis ◽

Triantafyllos Chavakis

Keyword(s):

Innate Immunity ◽

Progenitor Cells ◽

Immune Cells ◽

Innate Immune ◽

Hematopoietic Progenitor Cells ◽

Immune Memory ◽

Cardiometabolic Disease ◽

Innate Immune Cells ◽

Hematopoietic Progenitor ◽

Functional Changes

Until recently, immunologic memory was considered an exclusive characteristic of adaptive immunity. However, recent advances suggest that the innate arm of the immune system can also mount a type of nonspecific memory responses. Innate immune cells can elicit a robust response to subsequent inflammatory challenges after initial activation by certain stimuli, such as fungal-derived agents or vaccines. This type of memory, termed trained innate immunity (also named innate immune memory), is associated with epigenetic and metabolic alterations. Hematopoietic progenitor cells, which are the cells responsible for the generation of mature myeloid cells at steady-state and during inflammation, have a critical contribution to the induction of innate immune memory. Inflammation-triggered alterations in cellular metabolism, the epigenome and transcriptome of hematopoietic progenitor cells in the bone marrow promote long-lasting functional changes, resulting in increased myelopoiesis and consequent generation of trained innate immune cells. In the present brief review, we focus on the involvement of hematopoietic progenitors in the process of trained innate immunity and its possible role in cardiometabolic disease.

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Adaptive innate immunity or innate adaptive immunity?

Clinical Science ◽

10.1042/cs20180548 ◽

2019 ◽

Vol 133 (14) ◽

pp. 1549-1565 ◽

Cited By ~ 4

Author(s):

Jan Černý ◽

Ilja Stříž

Keyword(s):

Innate Immunity ◽

Adaptive Immunity ◽

Current Knowledge ◽

Cell Receptor ◽

Innate Immune ◽

Lymphoid Cells ◽

Immune Memory ◽

Cytotoxic Lymphocytes ◽

Black And White ◽

Pathogen Invasion

Abstract The innate immunity is frequently accepted as a first line of relatively primitive defense interfering with the pathogen invasion until the mechanisms of ‘privileged’ adaptive immunity with the production of antibodies and activation of cytotoxic lymphocytes ‘steal the show’. Recent advancements on the molecular and cellular levels have shaken the traditional view of adaptive and innate immunity. The innate immune memory or ‘trained immunity’ based on metabolic changes and epigenetic reprogramming is a complementary process insuring adaptation of host defense to previous infections. Innate immune cells are able to recognize large number of pathogen- or danger- associated molecular patterns (PAMPs and DAMPs) to behave in a highly specific manner and regulate adaptive immune responses. Innate lymphoid cells (ILC1, ILC2, ILC3) and NK cells express transcription factors and cytokines related to subsets of T helper cells (Th1, Th2, Th17). On the other hand, T and B lymphocytes exhibit functional properties traditionally attributed to innate immunity such as phagocytosis or production of tissue remodeling growth factors. They are also able to benefit from the information provided by pattern recognition receptors (PRRs), e.g. γδT lymphocytes use T-cell receptor (TCR) in a manner close to PRR recognition. Innate B cells represent another example of limited combinational diversity usage participating in various innate responses. In the view of current knowledge, the traditional black and white classification of immune mechanisms as either innate or an adaptive needs to be adjusted and many shades of gray need to be included.

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Induction of Trained Innate Immunity in Human Monocytes by Bovine Milk and Milk-Derived Immunoglobulin G

Nutrients ◽

10.3390/nu10101378 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1378 ◽

Cited By ~ 9

Author(s):

Marloes van Splunter ◽

Thijs van Osch ◽

Sylvia Brugman ◽

Huub Savelkoul ◽

Leo Joosten ◽

...

Keyword(s):

Innate Immunity ◽

Immunoglobulin G ◽

Cytokine Production ◽

Bovine Milk ◽

Innate Immune ◽

Immune Memory ◽

Bovine Lactoferrin ◽

Human Monocytes ◽

Trained Immunity

Innate immune memory, also termed “trained immunity” in vertebrates, has been recently described in a large variety of plants and animals. In most cases, trained innate immunity is induced by pathogens or pathogen-associated molecular patterns (PAMPs), and is associated with long-term epigenetic, metabolic, and functional reprogramming. Interestingly, recent findings indicate that food components can mimic PAMPs effects and induce trained immunity. The aim of this study was to investigate whether bovine milk or its components can induce trained immunity in human monocytes. To this aim, monocytes were exposed for 24 h to β-glucan, Toll-like receptor (TLR)-ligands, bovine milk, milk fractions, bovine lactoferrin (bLF), and bovine Immunoglobulin G (bIgG). After washing away the stimulus and a resting period of five days, the cells were re-stimulated with TLR ligands and Tumor necrosis factor (TNF-) and interleukin (IL)-6 production was measured. Training with β-glucan resulted in higher cytokine production after TLR1/2, TLR4, and TLR7/8 stimulation. When monocytes trained with raw milk were re-stimulated with TLR1/2 ligand Pam3CSK4, trained cells produced more IL-6 compared to non-trained cells. Training with bIgG resulted in higher cytokine production after TLR4 and TLR7/8 stimulation. These results show that bovine milk and bIgG can induce trained immunity in human monocytes. This confirms the hypothesis that diet components can influence the long-term responsiveness of the innate immune system.

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Rigidity of Cell Fate and Function Among Monocytes

Blood ◽

10.1182/blood-2021-151110 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2057-2057

Author(s):

Catherine Rhee ◽

Elizabeth W Scadden ◽

Lai Ping Wong ◽

Giulia Schiroli ◽

Michael Mazzola ◽

...

Keyword(s):

Innate Immunity ◽

Board Of Directors ◽

Myeloid Cells ◽

Innate Immune ◽

Immune Memory ◽

Publicly Traded ◽

Advisory Committees ◽

Adaptive Immune ◽

Classical Monocytes ◽

Privately Held

Abstract Myeloid cells are the most evolutionarily ancient aspect of a specialized immune system and the cornerstone of innate immunity in vertebrates. Innate immunity serves at the front line of host defense playing essential roles in directly clearing infection while also activating adaptive immune cell populations. Even with the importance in its roles, the myeloid system has often been regarded as the 'dumb brute' side of cell-based immunity with limited specificity and variability of responses. Heterogeneity in innate immune cells is increasingly recognized but still modest compared to other cell types and constrained by limited investigative tools. Monocytes have traditionally been categorized into two subsets: classical and non-classical. Classical monocytes are thought to readily convert to non-classical monocytes with exogenous cues. Studies on bulk monocyte populations have shown that monocytes acquire functional features dependent on physiological needs supporting a prevailing model that monocytes are highly plastic. We adapted a system for inducible clonal expansion of mouse granulocyte-monocyte progenitor (GMP) capable of differentiating into mature myeloid cells to address at a clonal level the issues of monocyte heterogeneity, plasticity, and whether changes in monocyte functional groups are due to induction or selection, Using inducible HoxB8-ER, large numbers of primary self-renewing GMP can undergo progressive maturation to fully functional granulocytes or monocytes upon removal of estrogen. The resulting GMP clones could then be characterized molecularly and immunophenotypically in correlation with the specialized functions of their descendent monocytes (Figure 1A). Four GMP differentiation trajectories that yield functionally distinct monocytes were defined (Figures 1B and 1C). Notably the functional monocyte groups were evident at the GMP level based on unsupervised clustering of chromatin configuration data (Figure 1D). GMP bore epigenetic scripting of the potential of their descendent monocytes and this fate had little flexibility once differentiation had begun. Testing cells under in vitro and in vivo homeostasis and stress conditions revealed that the cells maintain their differentiation path and do not transition from one state to another (Figures 1E and 1F). These data imply a model whereby monocyte stimulus-specific selection may occur and may contribute to an innate immune memory that resembles adaptive immune memory. Figure 1 Figure 1. Disclosures Sykes: Keros Therapeutics: Consultancy; SAFI Biosolutions: Consultancy, Current equity holder in publicly-traded company; Clear Creek Bio: Current equity holder in publicly-traded company. Scadden: Magenta Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Clear Creek Bio: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; LifeVaultBio: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Editas Medicines: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Current holder of individual stocks in a privately-held company; Clear Creek Bio: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Dainippon Sumitomo Pharma: Other: Sponsored research; FOG Pharma:: Consultancy; Garuda Therapeutics: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; VCanBio: Consultancy; Inzen Therapeutics: Membership on an entity's Board of Directors or advisory committees.

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