bims-traimu Biomed News
on Trained immunity
Issue of 2024–03–24
seven papers selected by
Yantong Wan, Southern Medical University
  1. Group 3 innate lymphoid cells: A trained Gutkeeper.
  2. Effectiveness of Universal BCG Immunisation in Reducing the Incidence and Mortality of COVID-19: A Secondary Data Analysis.
  3. Astrocyte cells in the brain have immune memory.
  4. Regulation of immune signal integration and memory by inflammation-induced chromosome conformation.
  5. 4-octyl itaconate alleviates cisplatin-induced ferroptosis possibly via activating the NRF2/HO-1 signalling pathway.
  6. Combinational delivery of TLR4 and TLR7/8 agonist enhanced the therapeutic efficacy of immune checkpoint inhibitors to colon tumor.
  7. Non-transcriptional IRF7 interacts with NF-κB to inhibit viral inflammation.
  1. Immunol Rev. 2024 Mar 16.
    Group 3 innate lymphoid cells: A trained Gutkeeper.
    Nicolas Serafini, James P Di Santo.
      Group 3 innate lymphoid cells (ILC3s) are tissue-resident immune lymphocytes that critically regulate intestinal homeostasis, organogenesis, and immunity. ILC3s possess the capacity to "sense" the inflammatory environment within tissues, especially in the context of pathogen challenges that imprints durable non-antigen-specific changes in ILC3 function. As such, ILC3s become a new actor in the emerging field of trained innate immunity. Here, we summarize recent discoveries regarding ILC3 responses to bacterial challenges and the role these encounters play in triggering trained innate immunity. We further discuss how signaling events throughout ILC3 ontogeny potentially control the development and function of trained ILC3s. Finally, we highlight the open questions surrounding ILC3 "training" the answers to which may reveal new insights into innate immunity. Understanding the fundamental concepts behind trained innate immunity could potentially lead to the development of new strategies for improving immunity-based modulation therapies for inflammation, infectious diseases, and cancer.
    Keywords:  ILC3; bacterial infection; innate immune memory; innate lymphoid cell; intestinal immunity; microbiota
    DOI:  https://doi.org/10.1111/imr.13322
  2. Niger Med J. 2021 Mar-Apr;62(2):62(2): 60-65
    Effectiveness of Universal BCG Immunisation in Reducing the Incidence and Mortality of COVID-19: A Secondary Data Analysis.
    Vikas Bhatia, Swayam Pragyan Parida, Durgesh Prasad Sahoo, Annu Antony, Arun Mitra.
       Background: Bacillus Calmette-Guérin (BCG) vaccine's immunomodulatory properties can protect against respiratory infections due to its nonspecific trained immunity of innate immune cells. The objective of the study is to assess the effectiveness of BCG in reducing incidence and morality of ongoing COVID-19 pandemic.
    Methodology: The present study is a secondary data analysis to compare the incidence and mortality of COVID 19 among countries who had BCG vaccine in their national immunisation schedule with other group of countries who did not have. Twenty-six countries with BCG vaccinations and eleven countries without BCG vaccinations were included in the analysis. The analysis was performed using the glmer() function in R and a random effects logistic model to study the determinants of incidence and mortality.
    Results: The association between the BCG vaccination and number of cases of COVID-19 was significant in the univariate analysis (p = 0.002), upon statistical adjustment; the random effects model shows there was no association between countries with BCG vaccine included in the national immunization schedule and the number of cases (p = 0.377). Similarly, BCG was not statistically associated with mortality (case fatality rate > 5%) with a p value of 0.443.
    Conclusion: Considering single variable BCG vaccine, the incidence and mortality of COVID-19 was found to be significantly higher in non-BCG vaccinated countries while no significant association was observed when other determinants were included affecting the epidemiology of COVID-19. Additional research is recommended, to study the relationship between BCG and COVID-19.
    Keywords:  Air Connectivity Index; BCG, COVID-19; Cases Per Million; Lockdown
  3. Nature. 2024 Mar 20.
    Astrocyte cells in the brain have immune memory.
    Michael V Sofroniew.
      
    Keywords:  Immunology; Neuroscience
    DOI:  https://doi.org/10.1038/d41586-024-00676-7
  4. bioRxiv. 2024 Mar 04. pii: 2024.02.29.582872. [Epub ahead of print]
    Regulation of immune signal integration and memory by inflammation-induced chromosome conformation.
    Bence Daniel, Andy Y Chen, Katalin Sandor, Wenxi Zhang, Zhuang Miao, Caleb A Lareau, Kathryn E Yost, Howard Y Chang, Ansuman T Satpathy.
      3-dimensional (3D) genome conformation is central to gene expression regulation, yet our understanding of its contribution to rapid transcriptional responses, signal integration, and memory in immune cells is limited. Here, we study the molecular regulation of the inflammatory response in primary macrophages using integrated transcriptomic, epigenomic, and chromosome conformation data, including base pair-resolution Micro-Capture C. We demonstrate that interleukin-4 (IL-4) primes the inflammatory response in macrophages by stably rewiring 3D genome conformation, juxtaposing endotoxin-, interferon-gamma-, and dexamethasone-responsive enhancers in close proximity to their cognate gene promoters. CRISPR-based perturbations of enhancer-promoter contacts or CCCTC-binding factor (CTCF) boundary elements demonstrated that IL-4-driven conformation changes are indispensable for enhanced and synergistic endotoxin-induced transcriptional responses, as well as transcriptional memory following stimulus removal. Moreover, transcriptional memory mediated by changes in chromosome conformation often occurred in the absence of changes in chromatin accessibility or histone modifications. Collectively, these findings demonstrate that rapid and memory transcriptional responses to immunological stimuli are encoded in the 3D genome.
    DOI:  https://doi.org/10.1101/2024.02.29.582872
  5. J Cell Mol Med. 2024 Apr;28(7): e18207
    4-octyl itaconate alleviates cisplatin-induced ferroptosis possibly via activating the NRF2/HO-1 signalling pathway.
    Li Zhang, Wenao Song, Hua Li, Xiaolin Cui, Jingyu Ma, Rongrong Wang, Yue Xu, Ming Li, Xiaohui Bai, Dawei Wang, Haihui Sun, Zhiming Lu.
      Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, plays a pivotal role in cisplatin-induced ototoxicity. Existing research has suggested that in cisplatin-mediated damage to auditory cells and hearing loss, ferroptosis is partially implicated. 4-Octyl itaconate (4-OI), derived from itaconic acid, effectively permeates cell membranes, showcasing potent anti-inflammatory as well as antioxidant effects in several disease models. Our study aimed to investigate the effect of 4-OI on cisplatin-induced ferroptosis and the underlying molecular mechanisms. The survival rates of HEI-OC1 cells and mice cochlea hair cells were measured by CCK8 and immunofluorescence, respectively. The auditory brainstem response (ABR) audiometry was used to detect changes in hearing thresholds in mice before and after treatment. Levels of ROS were evaluated by DCFH-DA. Real-time PCR quantified inflammatory cytokines TNF-α, IL-6 and IL-1β. Network Pharmacology and RNA sequencing (RNA-seq) analysis of the potential mechanism of 4-OI resistance to cisplatin-induced ferroptosis. The expressions of ferroptosis-related factors (GPX4, SLC7A11 and PTGS2) and important antioxidant factors (NRF2, HO-1, GCLC and NQO1) were tested by real-time PCR, Western blot and immunofluorescence. Results demonstrated cisplatin-induced significant ROS and inflammatory factor release, reduced NRF2 expression, hindered nuclear translocation and activated ferroptosis. Pretreatment with 4-OI exhibited anti-inflammatory and antioxidant effects, along with resistance to ferroptosis, ultimately mitigating cisplatin-induced cell loss. In the present study, we show that 4-OI inhibits cisplatin-induced ferroptosis possibly through activation of the NRF2/HO-1 signalling pathway, thereby exerting a protective effect against cisplatin-induced damage to auditory cells, and providing a new therapeutic strategy for cisplatin-induced hearing loss.
    Keywords:  4-octyl itaconate; NRF2; cisplatin; ferroptosis; ototoxicity
    DOI:  https://doi.org/10.1111/jcmm.18207
  6. Mol Cell Biochem. 2024 Mar 20.
    Combinational delivery of TLR4 and TLR7/8 agonist enhanced the therapeutic efficacy of immune checkpoint inhibitors to colon tumor.
    Mengjiao Wang, Quan Wan, Chenglv Wang, Qianyu Jing, Yujie Nie, Xiangyan Zhang, Xin Chen, De Yang, Runsang Pan, Linzhao Li, Lan Zhu, Huan Gui, Shuanghui Chen, Yuezhen Deng, Tao Chen, Yingjie Nie.
      Immunotherapy is regarded as a potent cancer treatment, with DC vaccines playing a crucial role. Although clinical trials have demonstrated the safety and efficacy of DC vaccines, loading antigens in vitro is challenging, and their therapeutic effects remain unpredictable. Moreover, the diverse subtypes and maturity states of DCs in the body could induce both immune responses and immune tolerance, potentially affecting the vaccine's efficacy. Hence, the optimization of DC vaccines remains imperative. Our study discovered a new therapeutic strategy by using CT26 and MC38 mouse colon cancer models, as well as LLC mouse lung cancer models. The strategy involved the synergistic activation of DCs through intertumoral administration of TLR4 agonist high-mobility group nucleosome binding protein 1 (HMGN1) and TLR7/8 agonist (R848/resiquimod), combined with intraperitoneal administration of TNFR2 immunosuppressant antibody. The experimental results indicated that the combined use of HMGN1, R848, and α-TNFR2 had no effect on LLC cold tumors. However, it was effective in eradicating CT26 and MC38 colon cancer and inducing long-term immune memory. The combination of these three drugs altered the TME and promoted an increase in anti-tumor immune components. This may provide a promising new treatment strategy for colon cancer.
    Keywords:  Combination immunotherapy; HMGN1; Immunosuppression; R848; α-TNFR2
    DOI:  https://doi.org/10.1007/s11010-024-04966-6
  7. J Biol Chem. 2024 Mar 18. pii: S0021-9258(24)01695-8. [Epub ahead of print] 107200
    Non-transcriptional IRF7 interacts with NF-κB to inhibit viral inflammation.
    Shumin Fan, Sonam Popli, Sukanya Chakravarty, Ritu Chakravarti, Saurabh Chattopadhyay.
      Interferon (IFN) regulatory factors (IRF) are key transcription factors in cellular antiviral responses. IRF7, a virus-inducible IRF, expressed primarily in myeloid cells, is required for transcriptional induction of IFNα and antiviral genes. IRF7 is activated by virus-induced phosphorylation in the cytoplasm, leading to its translocation to the nucleus for transcriptional activity. Here, we revealed a non-transcriptional activity of IRF7 contributing to its antiviral functions. IRF7 interacted with the pro-inflammatory transcription factor NF-κB-p65 and inhibited the induction of inflammatory target genes. Using knockdown, knockout, and overexpression strategies, we demonstrated that IRF7 inhibited NF-κB-dependent inflammatory target genes, induced by virus infection or toll-like receptor (TLR) stimulation. A mutant IRF7, defective in transcriptional activity, interacted with NF-κB-p65 and suppressed NF-κB-induced gene expression. A single-action IRF7 mutant, active in anti-inflammatory function, but defective in transcriptional activity, efficiently suppressed Sendai virus and murine hepatitis virus replication. We, therefore, uncovered an anti-inflammatory function for IRF7, independent of transcriptional activity, contributing to the antiviral response of IRF7.
    Keywords:  IRF7; NF-κB; antiviral; innate immunity; viral inflammation
    DOI:  https://doi.org/10.1016/j.jbc.2024.107200
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