bims-traimu Biomed News
on Trained immunity
Issue of 2022–07–10
seven papers selected by
Yantong Wan, Southern Medical University
  1. Mechanisms and Therapeutic Modulation of Neutrophil-Mediated Inflammation.
  2. Epigenetic modifications in metabolic memory: What are the memories, and can we erase them?
  3. Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells.
  4. Immunometabolic rewiring of tubular epithelial cells in kidney disease.
  5. Trained Immunity of IL-12-, IL-15-, and IL-18-Induced CD3+CD56+ NKT-Like Cells.
  6. Toll-like receptor (TLR) agonists as a driving force behind next-generation vaccine adjuvants and cancer therapeutics.
  7. The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles.
  1. J Dent Res. 2022 Jul 04. 220345221107602
    Mechanisms and Therapeutic Modulation of Neutrophil-Mediated Inflammation.
    G Hajishengallis, T Chavakis.
      Neutrophils are abundant, short-lived myeloid cells that are readily recruitable to sites of inflammation, where they serve as first-line defense against infection and other types of insult to the host. In recent years, there has been increased understanding on the involvement of neutrophils in chronic inflammatory diseases, where they may act as direct effectors of destructive inflammation. However, destructive tissue inflammation is also instigated in settings of neutrophil paucity, suggesting that neutrophils also mediate critical homeostatic functions. The activity of neutrophils is regulated by a variety of local tissue factors. In addition, systemic metabolic conditions, such as hypercholesterolemia and hyperglycemia, affect the production and mobilization of neutrophils from the bone marrow. Moreover, according to the recently emerged concept of innate immune memory, the functions of neutrophils can be enhanced through the process of trained granulopoiesis. This process may have both beneficial and potentially destructive effects, depending on context, that is, protective against infections and tumors, while destructive in the context of chronic inflammatory conditions. Although we are far from a complete understanding of the mechanisms underlying the regulation and function of neutrophils, current insights enable the development of targeted therapeutic interventions that can restrain neutrophil-mediated inflammation in chronic inflammatory diseases, such as periodontitis.
    Keywords:  complement; host modulation; metabolic dysregulation; myeloid cells; periodontitis; trained immunity
    DOI:  https://doi.org/10.1177/00220345221107602
  2. Am J Physiol Cell Physiol. 2022 Jul 04.
    Epigenetic modifications in metabolic memory: What are the memories, and can we erase them?
    Zhuo Chen, Rama Natarajan.
      Inherent and acquired abnormalities in gene regulation due to the influence of genetics and epigenetics (traits related to environment rather than genetic factors) underly many diseases including diabetes. Diabetes could lead to multiple complications including retinopathy, nephropathy and cardiovascular disease that greatly increase morbidity and mortality. Epigenetic changes have also been linked to diabetes-related complications. Genes associated with many pathophysiological features of these vascular complications (e.g., inflammation, fibrosis, and oxidative stress) can be regulated by epigenetic mechanisms involving histone posttranslational modifications, DNA methylation, changes in chromatin structure/remodeling and noncoding RNAs. Intriguingly, these epigenetic changes triggered during early periods of hyperglycemic exposure and uncontrolled diabetes are not immediately corrected even after restoration of normoglycemia and metabolic balance. This latency in effect across time and conditions is associated with persistent development of complications in diabetes with prior history of poor glycemic control, termed as metabolic memory or legacy effect. Epigenetic modifications are generally reversible and provide a window of therapeutic opportunity to ameliorate cellular dysfunction and mitigate or 'erase' metabolic memory. Notably, trained immunity and related epigenetic changes transmitted from hematopoietic stem cells to innate immune cells have also been implicated in metabolic memory. Hence, identification of epigenetic variations at candidate genes, or epigenetic signatures genome-wide by epigenome-wide association studies can aid in prompt diagnosis to prevent progression of complications and identification of much-needed new therapeutic targets. Herein, we provide a review of epigenetics and epigenomics in metabolic memory of diabetic complications covering the current basic research, clinical data, and translational implications.
    Keywords:  DNA methylation; Diabetic Complications; Epigenetics; Metabolic Memory
    DOI:  https://doi.org/10.1152/ajpcell.00201.2022
  3. Front Immunol. 2022 ;13 884148
    Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8+ T Cells.
    Marco Pio La Manna, Mojtaba Shekarkar Azgomi, Bartolo Tamburini, Giusto Davide Badami, Leila Mohammadnezhad, Francesco Dieli, Nadia Caccamo.
      The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases. Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as "memory". T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment. Phenotype, effector functions, maintenance, and metabolic pathways help identify these different subsets. Here, we examine recent developments in the characterization of the heterogeneity of the memory T cell compartment. In particular, we focus on the emerging role of CD8+ TRM and TSCM cells, providing evidence on how their immunometabolism or modulation can play a vital role in their generation and maintenance in chronic conditions such as infections or autoimmune diseases.
    Keywords:  CD8 TRM cells; CD8 TSCM cells; differentiation; infectious diseases; metabolism
    DOI:  https://doi.org/10.3389/fimmu.2022.884148
  4. Nat Rev Nephrol. 2022 Jul 07.
    Immunometabolic rewiring of tubular epithelial cells in kidney disease.
    Sanne van der Rijt, Jaklien C Leemans, Sandrine Florquin, Riekelt H Houtkooper, Alessandra Tammaro.
      Kidney tubular epithelial cells (TECs) have a crucial role in the damage and repair response to acute and chronic injury. To adequately respond to constant changes in the environment, TECs have considerable bioenergetic needs, which are supported by metabolic pathways. Although little is known about TEC metabolism, a number of ground-breaking studies have shown that defective glucose metabolism or fatty acid oxidation in the kidney has a key role in the response to kidney injury. Imbalanced use of these metabolic pathways can predispose TECs to apoptosis and dedifferentiation, and contribute to lipotoxicity and kidney injury. The accumulation of lipids and aberrant metabolic adaptations of TECs during kidney disease can also be driven by receptors of the innate immune system. Similar to their actions in innate immune cells, pattern recognition receptors regulate the metabolic rewiring of TECs, causing cellular dysfunction and lipid accumulation. TECs should therefore be considered a specialized cell type - like cells of the innate immune system - that is subject to regulation by immunometabolism. Targeting energy metabolism in TECs could represent a strategy for metabolically reprogramming the kidney and promoting kidney repair.
    DOI:  https://doi.org/10.1038/s41581-022-00592-x
  5. J Oncol. 2022 ;2022 8724933
    Trained Immunity of IL-12-, IL-15-, and IL-18-Induced CD3+CD56+ NKT-Like Cells.
    Siyu Zhu, Chen Zhang, Qian Sun, Yang Wang, Wenwen Yu, Feng Wei, Xiubao Ren.
      CD3+CD56+ natural killer T (NKT)-like cells have an immune function of T cells and NK cells, which play an important role in antitumor and antiviral immune responses. This study aims to establish a CD3+CD56+ NKT-like cell model by simulating the memory NK effect induced by cytokines IL-12, IL-15, and IL-18 (IL-12/15/18) and explore the formation mechanism. Our study found that the IL-12/15/18 preactivated CD3+CD56+ NKT-like cells exhibited enhanced IFN-γ production in response to restimulation with IL-12/15/18 for 6h on day 7. The intrinsic potential of these trained cells was significantly improved, showing an increase in IFN-γ, TNF-α, and cell proliferation potential. The IFN-γ release, granzyme B level, and proliferation ability significantly increased when stimulated by NK-cell-sensitive K562 tumor cells. Among these cytokines, the combination of IL-12/15/18 was particularly effective. After the preactivation of IL-12/15/18, some cell surface proteins related to function and differentiation, such as CD11b, CD62 L, NKp46, NKG2A, and CD127, showed an evident and consistent change trend. The CDK4/6 inhibitor can effectively weaken this effect, and the expression of cyclin D1, Rb protein phosphorylation, and E2F-1 decreased significantly. Our work revealed that cytokine IL-12/15/18 can induce CD3+CD56+ NKT-like cells to obtain enhanced training immunity, which was a memory-like phenomenon.
    DOI:  https://doi.org/10.1155/2022/8724933
  6. Curr Opin Chem Biol. 2022 Jul 01. pii: S1367-5931(22)00057-6. [Epub ahead of print]70 102172
    Toll-like receptor (TLR) agonists as a driving force behind next-generation vaccine adjuvants and cancer therapeutics.
    Arshpreet Kaur, Jeremy Baldwin, Deshkanwar Brar, Deepak B Salunke, Nikolai Petrovsky.
      Until recently, the development of new human adjuvants was held back by a poor understanding of their mechanisms of action. The field was revolutionized by the discovery of the toll-like receptors (TLRs), innate immune receptors that directly or indirectly are responsible for detecting pathogen-associated molecular patterns (PAMPs) and respond to them by activating innate and adaptive immune pathways. Hundreds of ligands targeting various TLRs have since been identified and characterized as vaccine adjuvants. This work has important implications not only for the development of vaccines against infectious diseases but also for immuno-therapies against cancer, allergy, Alzheimer's disease, drug addiction and other diseases. Each TLR has its own specific tissue localization and downstream gene signalling pathways, providing researchers the opportunity to precisely tailor adjuvants with specific immune effects. TLR agonists can be combined with other TLR or alternative adjuvants to create combination adjuvants with synergistic or modulatory effects. This review provides an introduction to the various classes of TLR adjuvants and their respective signalling pathways. It provides an overview of recent advancements in the TLR field in the past 2-3 years and discusses criteria for selecting specific TLR adjuvants based on considerations, such as disease mechanisms and correlates of protection, TLR immune biasing capabilities, route of administration, antigen compatibility, new vaccine technology platforms, and age- and species-specific effects.
    Keywords:  Adjuvant; Immune bias; TLR signalling; Toll-like receptor; Vaccine
    DOI:  https://doi.org/10.1016/j.cbpa.2022.102172
  7. Nanomaterials (Basel). 2022 Jul 05. pii: 2307. [Epub ahead of print]12(13):
    The TLR4/NFκB-Dependent Inflammatory Response Activated by LPS Is Inhibited in Human Macrophages Pre-Exposed to Amorphous Silica Nanoparticles.
    Massimiliano G Bianchi, Martina Chiu, Giuseppe Taurino, Enrico Bergamaschi, Francesco Cubadda, Guido M Macaluso, Ovidio Bussolati.
      Amorphous silica nanoparticles (ASNP) are present in a variety of products and their biological effects are actively investigated. Although several studies have documented pro-inflammatory effects of ASNP, the possibility that they also modify the response of innate immunity cells to natural activators has not been thoroughly investigated. Here, we study the effects of pyrogenic ASNP on the LPS-dependent activation of human macrophages differentiated from peripheral blood monocytes. In macrophages, 24 h of pre-exposure to non-cytotoxic doses of ASNP markedly inhibited the LPS-dependent induction of pro-inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10). The inhibitory effect was associated with the suppression of NFκB activation and the increased intracellular sequestration of the TLR4 receptor. The late induction of glutamine synthetase (GS) by LPS was also prevented by pre-exposure to ASNP, while GS silencing did not interfere with cytokine secretion. It is concluded that (i) macrophages exposed to ASNP are less sensitive to LPS-dependent activation and (ii) GS induction by LPS is likely secondary to the stimulation of cytokine secretion. The observed interference with LPS effects may point to a dampening of the acute inflammatory response after exposure to ASNP in humans.
    Keywords:  autophagy; endotoxin; glutamine synthetase; inflammation; monocyte-derived macrophages; synthetic amorphous silica (SAS); toll-like receptor 4
    DOI:  https://doi.org/10.3390/nano12132307
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