bims-traimu Biomed News
on Trained immunity
Issue of 2023‒01‒01
five papers selected by
Yantong Wan
Southern Medical University


  1. Clin Immunol. 2022 Dec 21. pii: S1521-6616(22)00289-3. [Epub ahead of print]246 109208
      The innate immune system can display heterologous memory-like responses termed trained immunity after stimulation by certain vaccinations or infections. In this randomized, placebo-controlled trial, we investigated the modulation of Bacille Calmette-Guérin (BCG)-induced trained immunity by BCG revaccination or high-dose BCG administration, in comparison to a standard dose. We show that monocytes from all groups of BCG-vaccinated individuals exerted increased TNFα production after ex-vivo stimulation with various unrelated pathogens. Similarly, we observed increased amounts of T-cell-derived IFNγ after M. tuberculosis exposure, regardless of the BCG intervention. NK cell cytokine production, especially after heterologous stimulation with the fungal pathogen Candida albicans, was predominantly boosted after high dose BCG administration. Cytokine production capacity before vaccination was inversely correlated with trained immunity. While the induction of a trained immunity profile is largely dose- or frequency independent, baseline cytokine production capacity is associated with the magnitude of the innate immune memory response after BCG vaccination.
    Keywords:  Bacille Calmette-Guérin; Booster; Innate immune memory; Mycobacterium tuberculosis; Non-specific beneficial effects; Revaccination
    DOI:  https://doi.org/10.1016/j.clim.2022.109208
  2. CNS Neurol Disord Drug Targets. 2022 Dec 23.
      Bacillus Calmette-Guérin (BCG) is the first developed vaccine to prevent tuberculosis (TB) and is the world's most widely used vaccine. It has a reconcilable defense in opposition to tuberculosis, meningitis, and miliary disease in children but changeable protection against pulmonary TB. Immune activation is responsible for regulating neural development by activating it. The effect of the BCG vaccine on neuronal disorders due to subordinate immune provocation is useful. BCG vaccine can prevent neuronal degeneration in different neurological disorders by provoking auto-reactive T-cells. In the case of TB, CD4+ T-cells effectively protect the immune response by protecting the central defense. Because of the preceding fact, BCG induces protection by creating precise T-cells like CD4+ T-cells and CD8+ T-cells. Hence, vaccination-induced protection generates specific T-cells and CD4+ T-cells, and CD8+ T-cells. The BCG vaccine may have an essential effect on motor disorders and play a crucial role in neuroprotective management. The present review describes how the BCG vaccine might be interrelated with motor disorders and play a key role in such diseases.
    Keywords:  Autoimmunity; BCG Vaccine; Movement Disorders; Neuroinflammation; Neuroprotection; PD.
    DOI:  https://doi.org/10.2174/1871527322666221223142813
  3. J Invertebr Pathol. 2022 Dec 21. pii: S0022-2011(22)00158-6. [Epub ahead of print]197 107872
      To prevent loss from disease, immunostimulants have been used as dietary supplements to improve immunity and survival of shrimps. Among the various types of immunostimulants, there is increasing evidence that a diet enriched with bacterial lipopolysaccharide can reduce the mortality rate of shrimp under exposure to pathogens. Here, the immunostimulatory effects of bacterial lipopolysaccharide (LPS) from various bacterial sources were explored. Bacterial LPS was extracted from a shrimp pathogen, Vibrio harveyi and its effects were compared with the commercially available LPS from the non-shrimp pathogen, Escherichia coli. Our results revealed that the LPS from V. harveyi was different in molecular size but contained similar functional groups to that from E. coli. To understand their molecular mechanisms, bacterial LPS from the two sources were applied as a supplementary diet and fed to juvenile shrimp for 4-week feeding period before tissue samples were collected for transcriptomic analysis by next generation sequencing. Gene expression profiling revealed that major immune-related genes such as pattern recognition proteins (PRPs), proteinases and proteinase inhibitors, prophenoloxidase systems (proPO system), antimicrobial peptides (AMPs), signaling transduction pathways, heat shock proteins (HSPs), oxidative stress responses, and other immune-related molecules such as mucins and peritrophins were modulated in the groups of shrimp fed with bacterial LPS from both sources, but at different levels. The results suggest that bacterial LPS could modulate shrimp immune system, and different LPS sources led to different activation of immune pathways. Additionally, metabolic-related genes were affected by LPS, suggesting that energy was required for immune stimulation. In the V. harveyi pathogen challenge trial, all shrimp groups fed with diets containing LPS from both bacterial sources showed better survival than the control group without LPS. When comparing groups fed with LPS supplemented diets, the higher concentration of LPS (8 μg/body weight) from E. coli resulted in a better survival rate than a lower concentration (4 μg/body weight). Conversely, shrimp fed with a diet containing LPS from V. harveyi showed a lower survival rate when a higher dose of LPS (8 μg/body weight) was administered than the group fed with a lower concentration of LPS (4 μg/body weight). This could be due to overstimulation of shrimp immune responses, especially by LPS derived from shrimp pathogens, resulting in a reverse effect. These results confirm that immunity in shrimp upon administration of bacterial LPS depends on the origin and dose of the LPS administered.
    Keywords:  Immunostimulant; Lipopolysaccharides; Penaeus monodon; Shrimp; Transcriptome; Vibrio harveyi
    DOI:  https://doi.org/10.1016/j.jip.2022.107872
  4. Front Plant Sci. 2022 ;13 1075279
      Understanding plant stress memory under extreme temperatures such as cold and heat could contribute to plant development. Plants employ different types of stress memories, such as somatic, intergenerational and transgenerational, regulated by epigenetic changes such as DNA and histone modifications and microRNAs (miRNA), playing a key role in gene regulation from early development to maturity. In most cases, cold and heat stresses result in short-term epigenetic modifications that can return to baseline modification levels after stress cessation. Nevertheless, some of the modifications may be stable and passed on as stress memory, potentially allowing them to be inherited across generations, whereas some of the modifications are reactivated during sexual reproduction or embryogenesis. Several stress-related genes are involved in stress memory inheritance by turning on and off transcription profiles and epigenetic changes. Vernalization is the best example of somatic stress memory. Changes in the chromatin structure of the Flowering Locus C (FLC) gene, a MADS-box transcription factor (TF), maintain cold stress memory during mitosis. FLC expression suppresses flowering at high levels during winter; and during vernalization, B3 TFs, cold memory cis-acting element and polycomb repressive complex 1 and 2 (PRC1 and 2) silence FLC activation. In contrast, the repression of SQUAMOSA promoter-binding protein-like (SPL) TF and the activation of Heat Shock TF (HSFA2) are required for heat stress memory. However, it is still unclear how stress memory is inherited by offspring, and the integrated view of the regulatory mechanisms of stress memory and mitotic and meiotic heritable changes in plants is still scarce. Thus, in this review, we focus on the epigenetic regulation of stress memory and discuss the application of new technologies in developing epigenetic modifications to improve stress memory.
    Keywords:  DNA methylation; chromatin remodelling; epigenetics; histone modifications; intergenerational memory; somatic memory; stress memory; transgenerational memory
    DOI:  https://doi.org/10.3389/fpls.2022.1075279
  5. Aliment Pharmacol Ther. 2022 Dec 31.
      BACKGROUND: Natural killer (NK) cells exhibit a selective deficiency of IFN-γ production in chronic hepatitis B (CHB). Toll-like receptor 8 (TLR8) agonists could induce IFN-γ production in immune cells, although their effects on the deficiency in NK cells remain unclear.AIMS: To investigate TLR8 expression in NK cells and the effect of TLR8 agonists in patients with CHB METHODS: We enrolled 32 patients with CHB and 19 healthy controls to assess TLR8 expression and IFN-γ production in NK cells. The sorted NK cells and monocytes were co-cultured to compare the extent of IFN-γ and IL-10 production after TLR8 agonist ssRNA40 stimulation. The synergic effect of NK cells and monocytes was assessed by blocking IL-12 and IL-18. We recruited another 22 patients with CHB undergoing nucleotide analogue (NA) therapy to explore the impact of antiviral treatment on the ssRNA40-mediated response of NK cells.
    RESULTS: In patients with CHB, TLR8 expression in NK cells was up-regulated, accompanied by insufficient IFN-γ production. The enhanced IFN-γ secretion by ssRNA40 in NK cells depended on monocyte-derived IL-12 and IL-18. NK cells displayed an imbalanced response to ssRNA40 in patients with CHB with a weak increase in IFN-γ despite a higher IL-10 production. The response was improved in patients with CHB undergoing NA therapy.
    CONCLUSIONS: In patients with CHB, targeting TLR8 partially rescues the IFN-γ insufficiency in NK cells. However, NK cells show an inhibitory response to TLR8 agonist stimulation. TLR8 agonist combined with NA may enhance the antiviral effect of NK cells.
    Keywords:  IFN-γ; IL-10; TLR8; chronic hepatitis B; natural killer cells
    DOI:  https://doi.org/10.1111/apt.17382