bims-traimu Biomed News
on Trained immunity
Issue of 2024–12–01
seven papers selected by
Yantong Wan, Southern Medical University
  1. The immune memory of innate immune systems.
  2. Parent-Specific Transgenerational Immune Priming Enhances Offspring Defense-Unless Heat Stress Negates It All.
  3. A polycomb group protein EED epigenetically regulates responses in lipopolysaccharide tolerized macrophages.
  4. Targeting Sepsis: Disease Tolerance, Immune Resilience, and Compartmentalized Immunity.
  5. SARS-CoV-2 reprograms murine alveolar macrophages to dampen flu.
  6. [Advancements in the regulatory effects and mechanisms of the immune metabolite itaconate in diseases].
  7. [A DC-iDEP-based fast and high-resolution method for detection of LPS tolerance of RAW264.7 macrophages and screening of therapeutic agents].
  1. Int Immunol. 2024 Nov 26. pii: dxae067. [Epub ahead of print]
    The immune memory of innate immune systems.
    Yasuhiro Kato, Atsushi Kumanogoh.
      Immune memory has long been considered a function specific to adaptive immune systems; however, adaptive immune memory alone has not fully explained the mechanism by which vaccines exert their protective effects against non-target pathogens. Recently, trained immunity, in which human monocytes vaccinated with bacillus Calmette-Guérin become highly responsive to pathogens other than Mycobacterium tuberculosis, has been reported. However, a phenomenon called endotoxin tolerance is also known, in which monocyte responsiveness is attenuated after the first lipopolysaccharide stimulation. These phenomena represent an altered innate immune response after the initial exposure to the stimulus, indicating that memories are formed in the innate immune system. In this review, we discuss trained immunity and endotoxin tolerance, known as innate immune memory, and innate immune memory formation by mRNA vaccines, which have been newly used in the COVID-19 pandemic and are considered important vaccine modalities in the future.
    Keywords:  Endotoxin tolerance; Epigenetic reprogramming; Trained immunity
    DOI:  https://doi.org/10.1093/intimm/dxae067
  2. Ecol Evol. 2024 Nov;14(11): e70552
    Parent-Specific Transgenerational Immune Priming Enhances Offspring Defense-Unless Heat Stress Negates It All.
    Ralf F Schneider, Arseny Dubin, Silke-Mareike Marten, Olivia Roth.
      Transgenerational immune priming (TGIP) adjusts offspring's immune responses based on parental immunological experiences. It is predicted to be adaptive when parent-offspring environmental conditions match, while mismatches negate those advantages, rendering TGIP potentially costly. We tested these cost-benefit dynamics in the pipefish Syngnathus typhle (Syngnathidae). Because of their unique male pregnancy, egg production and rearing occur in different sexes, providing both parents multiple avenues for TGIP. Parental bacteria exposure in our pipefish was simulated through vaccinations with heat-killed Vibrio aestuarianus before mating the fish to each other or to controls. The resulting offspring were exposed to V. aestuarianus in control or heat stress environments, after which transcriptome and microbiome compositions were investigated. Transcriptomic TGIP effects were only observed in Vibrio-exposed offspring at control temperatures, arguing for low costs of TGIP in non-matching microbiota environments. Transcriptomic phenotypes elicited by maternal and paternal TGIP had limited overlap and were not additive. Parentally induced transcriptomic responses were associated with immune functions, and specifically, the paternal response to the innate immune branch, possibly hinting at trained immunity. TGIP of both parents reduced the relative abundance of the experimental Vibrio in exposed offspring, showcasing its ecological benefits. Despite TGIP's significance in matching biotic environments, no TGIP-associated phenotypes were observed for heat-treated offspring, illustrating its limitations. Heat spikes caused by climate change thus threaten TGIP benefits, potentially increasing susceptibility to emerging marine diseases. We demonstrate the urgent need to understand how animals cope with climate-induced changes in microbial assemblages to assess their vulnerability in light of climate change.
    Keywords:  Syngnathus typhle; broad‐nosed pipefish; ecology; microbiome; trained immunity; transcriptome
    DOI:  https://doi.org/10.1002/ece3.70552
  3. Epigenetics Chromatin. 2024 Nov 29. 17(1): 36
    A polycomb group protein EED epigenetically regulates responses in lipopolysaccharide tolerized macrophages.
    Atsadang Boonmee, Salisa Benjaskulluecha, Patipark Kueanjinda, Benjawan Wongprom, Thitiporn Pattarakankul, Kittitach Sri-Ngern-Ngam, Supawadee Umthong, Junichiro Takano, Haruhiko Koseki, Tanapat Palaga.
       BACKGROUND: To avoid exaggerated inflammation, innate immune cells adapt to become hypo-responsive or "tolerance" in response to successive exposure to stimuli, which is a part of innate immune memory. Polycomb repressive complex 2 (PRC2) mediates the transcriptional repression by catalyzing histone H3 lysine 27 trimethylation (H3K27me3) but little is known about its role in lipopolysaccharide (LPS)-induced tolerance in macrophages.
    RESULT: We examined the unexplored roles of EED, a component of the PRC2, in LPS tolerant macrophages. In Eed KO macrophages, significant reduction in H3K27me3 and increased active histone mark, H3K27ac, was observed. Eed KO macrophages exhibited dampened pro-inflammatory cytokine productions (TNF-α and IL-6) while increasing non-tolerizable genes upon LPS tolerance. Pharmacological inhibition of EED also reduced TNF-α and IL-6 during LPS tolerance. Mechanistically, LPS tolerized Eed KO macrophages failed to increase glycolytic activity. RNA-Seq analyses revealed that the hallmarks of hypoxia, TGF-β, and Wnt/β-catenin signaling were enriched in LPS tolerized Eed KO macrophages. Among the upregulated genes, the promoter of Runx3 was found to be associated with EED. Silencing Runx3 in Eed KO macrophages partially rescued the dampened pro-inflammatory response during LPS tolerance. Enrichment of H3K27me3 was decreased in a subset of genes that are upregulated in Eed KO LPS tolerized macrophages, indicating the direct regulatory roles of PRC2 on such genes. Motif enrichment analysis identified the ETS family transcription factor binding sites in the absence of EED in LPS tolerized macrophages.
    CONCLUSION: Our results provided mechanistic insight into how the PRC2 via EED regulates LPS tolerance in macrophages by epigenetically silencing genes that play a crucial role during LPS tolerance such as those of the TGF-β/Runx3 axis.
    Keywords:  EED; Epigenetics; LPS-induced tolerant macrophages; PRC2 complex
    DOI:  https://doi.org/10.1186/s13072-024-00562-6
  4. Biomedicines. 2024 Oct 22. pii: 2420. [Epub ahead of print]12(11):
    Targeting Sepsis: Disease Tolerance, Immune Resilience, and Compartmentalized Immunity.
    Alexis Garduno, Ignacio Martín-Loeches.
      Introduction: Sepsis remains a major contributor to critical care mortality and morbidity worldwide. Despite advances in understanding its complex immunopathology, the compartmentalized nature of immune responses across different organs has yet to be fully translated into targeted therapies. This review explores the burden of sepsis on organ-specific immune dysregulation, immune resilience, and epigenetic reprogramming, emphasizing translational challenges and opportunities. Methods: We implemented a systematic literature search strategy, incorporating data from studies published between 2010 and 2024, to evaluate the role of molecular profiling techniques, including transcriptomics and epigenetic markers, in assessing the feasibility of targeted therapies. Results: Sepsis-induced immune dysregulation manifests differently in various organs, with lung, heart, liver, and kidney responses driven by unique local immune environments. Organ-specific biomarkers, such as the Spns2/S1P axis in lung macrophages, mitochondrial dysfunction in the heart, proenkephalin for early acute kidney injury (AKI), and adrenomedullin for predicting multi-organ failure, offer promising avenues for timely intervention. Furthermore, immune resilience, particularly through regulatory T-cell modulation and cytokine targeting (e.g., IL-18), is crucial for long-term recovery. Epigenetic mechanisms, including histone modification and trained immunity, present opportunities for reprogramming immune responses but require more precision to avoid unintended inflammatory sequelae. Conclusions: A deeper understanding of compartmentalized immune responses and the dynamic immune landscape in sepsis is critical for developing precision therapies. Real-time immune monitoring and organ-targeted interventions could revolutionize sepsis management, although significant barriers remain in clinical translation. Further research is required to establish biomarkers and treatment timing that optimize therapeutic efficacy while minimizing systemic risks.
    Keywords:  compartmentalized immune responses; critical care; epigenetics; immune dysregulation; immune resilience; organ-specific therapy; sepsis
    DOI:  https://doi.org/10.3390/biomedicines12112420
  5. Trends Immunol. 2024 Nov 22. pii: S1471-4906(24)00273-4. [Epub ahead of print]
    SARS-CoV-2 reprograms murine alveolar macrophages to dampen flu.
    Alexandra Tabachnikova, Akiko Iwasaki.
      Innate immune cells that are epigenetically reprogrammed by infection can modify host responses to subsequent infections. Lercher et al. have identified epigenetic reprogramming of murine airway-resident macrophages following recovery from SARS-CoV-2 infection, conferring protection from pathology and lethality following secondary influenza A virus (IAV) challenge without reducing viral titers.
    DOI:  https://doi.org/10.1016/j.it.2024.11.002
  6. Sheng Wu Gong Cheng Xue Bao. 2024 Nov 25. 40(11): 3888-3901
    [Advancements in the regulatory effects and mechanisms of the immune metabolite itaconate in diseases].
    Zhongkun Cheng, Jingxian Zhao, Yanyan Liu, Ling Xu, Guangwei Zhao, Xingwei Ni, Xiaowei Yang.
      Itaconate is a pivotal intermediate metabolite in the tricarboxylic acid (TCA) cycle of immune cells. It is produced by decarboxylation of cis-aconitic acid under the catalysis of aconitate decarboxylase 1 (ACOD1), which is encoded by the immune response gene 1 (IRG1). Itaconate has become a focal point of research on immunometabolism. Studies have demonstrated that itaconate plays a crucial role in diseases by regulating inflammation, remodeling cell metabolism, and participating in epigenetic regulation. This paper reviewed the research progress in itaconnate from its chemical structure, regulatory effects on different diseases, and mechanisms, proposes the future research directions, aiming to provide a theoretical basis for the development of itaconate-related drugs.
    Keywords:  cell metabolism; genetic regulation; immunization; inflammation; itaconate; metabolites
    DOI:  https://doi.org/10.13345/j.cjb.240328
  7. Sheng Wu Gong Cheng Xue Bao. 2024 Nov 25. 40(11): 4149-4156
    [A DC-iDEP-based fast and high-resolution method for detection of LPS tolerance of RAW264.7 macrophages and screening of therapeutic agents].
    Yameng Liu, Miaomiao Wang.
      Sepsis is a leading life-threatening problem in intensive care medicine. The recent studies have given insights into the transition from inflammation to long-term immunosuppression in sepsis. This condition might cause physiological changes that comprise the lipopolysaccharide (LPS) tolerance. Most studies about the LPS tolerance focus on the reduced ability of macrophages to secrete pro-inflammatory cytokines. Although this method has identified various molecular changes, it remains ambiguous since changes in the whole cell population are measured as an average and markers are required for cell recognition. A fast and label-free method is in demand to detect cell tolerance and screen therapeutic agents that might reverse the process. In this study, direct current insulator-based dielectrophoresis (DC-iDEP) was used to characterize the biophysical properties (EKMr) of inflamed cells, LPS-tolerant cells, and cells treated with therapeutic agents. The results showed that the EKMr of these cells was 4.28×108, 3.13×108, and 4.25×108 V/m2, respectively, suggesting that the established method was useful in distinguishing LPS-tolerant cells. The device holds the promise to be applied in medical diagnosis and medicine screening.
    Keywords:  direct current insulator-based dielectrophoresis (DC-iDEP); immune tolerance; medicine screening; microfluidics
    DOI:  https://doi.org/10.13345/j.cjb.240200
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