bims-traimu Biomed News
on Trained immunity
Issue of 2024‒05‒05
six papers selected by
Yantong Wan, Southern Medical University
  1. Induction of trained immunity using β-glucan and its protective responses in Nile tilapia, Oreochromis niloticus.
  2. The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum.
  3. Sepsis-trained macrophages promote antitumoral tissue-resident T cells.
  4. Dietary Intake of Yeast-Derived β-Glucan and Rice-Derived Arabinoxylan Induces Dose-Dependent Innate Immune Priming in Mice.
  5. N4BP1 coordinates ubiquitin-dependent crosstalk within the IκB kinase family to limit Toll-like receptor signaling and inflammation.
  6. Inhibitory mechanisms of decoy receptor 3 in cecal ligation and puncture-induced sepsis.
  1. Dev Comp Immunol. 2024 Apr 25. pii: S0145-305X(24)00060-0. [Epub ahead of print]157 105188
    Induction of trained immunity using β-glucan and its protective responses in Nile tilapia, Oreochromis niloticus.
    David Waikhom, Jeena Kezhedath, Sooraj Nediyirippil Suresh, Megha Kadam Bedekar, Tincy Varghese, Pani Prasad Kurcheti, Rajendran Kooloth Valappil.
      Emerging and re-emerging diseases in fish cause drastic economic losses in the aquaculture sector. To combat the impact of disease outbreaks and prevent the emergence of infections in culture systems, understanding the advanced strategies for protecting fish against infections is inevitable in fish health research. Therefore, the present study aimed to evaluate the induction of trained immunity and its protective efficacy against Streptococcus agalactiae in tilapia. For this, Nile tilapia and the Tilapia head kidney macrophage primary culture were primed using β-glucan @200 μg/10 g body weight and 10 μg/mL respectively. Expression profiles of the markers of trained immunity and production of metabolites were monitored at different time points, post-priming and training, which depicted enhanced responsiveness. Higher lactate and lactate dehydrogenase (LDH) production in vitro suggests heightened glycolysis induced by priming of the cells using β-glucan. A survival rate of 60% was observed in β-glucan trained fish post challenge with virulent S. agalactiae at an LD50 of 2.6 × 107 cfu/ml, providing valuable insights into promising strategies of trained immunity for combating infections in fish.
    Keywords:  Glucan; Innate immune memory; Nile tilapia; Streptococcus agalactiae; Trained immunity
    DOI:  https://doi.org/10.1016/j.dci.2024.105188
  2. BMC Immunol. 2024 Apr 30. 25(1): 24
    The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum.
    N L Messina, M Wang, E K Forbes, B Freyne, W P Hasang, S Germano, R Bonnici, F Summons, K Gardiner, S Donath, R Gordon, S J Rogerson, N Curtis.
      BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against malaria. We investigated whether BCG vaccination influences neonatal in vitro cytokine responses to Plasmodium falciparum. Blood samples were collected from 108 participants in the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial (Clinical trials registration NCT01906853, registered July 2013), seven days after randomisation to neonatal BCG (n = 66) or no BCG vaccination (BCG-naïve, n = 42). In vitro cytokine responses were measured following stimulation with P. falciparum-infected erythrocytes (PfIE) or E. coli.RESULTS: No difference in the measured cytokines were observed between BCG-vaccinated and BCG-naïve neonates following stimulation with PfIE or E. coli. However, age at which blood was sampled was independently associated with altered cytokine responses to PfIE. Being male was also independently associated with increased TNF-a responses to both PfIE and E. coli.
    CONCLUSION: These findings do not support a role for BCG vaccination in influencing in vitro neonatal cytokine responses to P. falciparum. Older neonates are more likely to develop P. falciparum-induced IFN-γ and IFN-γ-inducible chemokine responses implicated in early protection against malaria and malaria pathogenesis.
    Keywords:  BCG; Cytokine; Immunity; Malaria; Neonate; Non-specific effects; Plasmodium falciparum
    DOI:  https://doi.org/10.1186/s12865-024-00611-5
  3. Nat Immunol. 2024 May;25(5): 802-819
    Sepsis-trained macrophages promote antitumoral tissue-resident T cells.
    Alexis Broquet, Victor Gourain, Thomas Goronflot, Virginie Le Mabecque, Debajyoti Sinha, Mitra Ashayeripanah, Cédric Jacqueline, Pierre Martin, Marion Davieau, Lea Boutin, Cecile Poulain, Florian P Martin, Cynthia Fourgeux, Melanie Petrier, Manon Cannevet, Thomas Leclercq, Maeva Guillonneau, Tanguy Chaumette, Thomas Laurent, Christelle Harly, Emmanuel Scotet, Laurent Legentil, Vincent Ferrières, Stephanie Corgnac, Fathia Mami-Chouaib, Jean Francois Mosnier, Nicolas Mauduit, Hamish E G McWilliam, Jose A Villadangos, Pierre Antoine Gourraud, Karim Asehnoune, Jeremie Poschmann, Antoine Roquilly.
      Sepsis induces immune alterations, which last for months after the resolution of illness. The effect of this immunological reprogramming on the risk of developing cancer is unclear. Here we use a national claims database to show that sepsis survivors had a lower cumulative incidence of cancers than matched nonsevere infection survivors. We identify a chemokine network released from sepsis-trained resident macrophages that triggers tissue residency of T cells via CCR2 and CXCR6 stimulations as the immune mechanism responsible for this decreased risk of de novo tumor development after sepsis cure. While nonseptic inflammation does not provoke this network, laminarin injection could therapeutically reproduce the protective sepsis effect. This chemokine network and CXCR6 tissue-resident T cell accumulation were detected in humans with sepsis and were associated with prolonged survival in humans with cancer. These findings identify a therapeutically relevant antitumor consequence of sepsis-induced trained immunity.
    DOI:  https://doi.org/10.1038/s41590-024-01819-8
  4. Mol Nutr Food Res. 2024 Apr 29. e2300829
    Dietary Intake of Yeast-Derived β-Glucan and Rice-Derived Arabinoxylan Induces Dose-Dependent Innate Immune Priming in Mice.
    Bart G J Moerings, Jurriaan J Mes, Jeroen van Bergenhenegouwen, Coen Govers, Miriam van Dijk, Renger F Witkamp, Klaske van Norren, Suzanne Abbring.
      Beta-glucans and arabinoxylans are known for their immunostimulatory properties. However, in vivo these have been documented almost exclusively following parenteral administration, underemphasizing oral intake. C57BL/6 mice are fed either a control diet or a diet supplemented with yeast-derived whole β-glucan particle (yWGP) or with rice-derived arabinoxylan (rice bran-1) at a concentration of 1%, 2.5%, or 5% weight/weight (w/w) for 2 weeks. Thereafter, cells from blood, bone marrow, and spleen are collected for ex vivo stimulation with various microbial stimuli. Dietary intake of yWGP for 2 weeks at concentrations of 1% and 2.5% w/w increases ex vivo cytokine production in mouse blood and bone marrow, whereas 5% w/w yWGP shows no effect. In the spleen, cytokine production remains unaffected by yWGP. At a concentration of 1% w/w, rice bran-1 increases ex vivo cytokine production by whole blood, but 2.5% and 5% w/w cause inhibitory effects in bone marrow and spleen. This study demonstrates that dietary yWGP and rice bran-1 induce immune priming in mouse blood and bone marrow, with the strongest effects observed at 1% w/w. Future human trials should substantiate the efficacy of dietary β-glucans and arabinoxylans to bolster host immunity, focusing on dose optimization.
    Keywords:  arabinoxylan; dietary intake; dose optimization; innate immune priming ; β‐glucan
    DOI:  https://doi.org/10.1002/mnfr.202300829
  5. Immunity. 2024 Apr 26. pii: S1074-7613(24)00209-7. [Epub ahead of print]
    N4BP1 coordinates ubiquitin-dependent crosstalk within the IκB kinase family to limit Toll-like receptor signaling and inflammation.
    Alexander D Gitlin, Allie Maltzman, Yuzuka Kanno, Klaus Heger, Rohit Reja, Alexander F Schubert, Linsey J Wierciszewski, Homer Pantua, Sharookh B Kapadia, Seth F Harris, Joshua D Webster, Kim Newton, Vishva M Dixit.
      The ubiquitin-binding endoribonuclease N4BP1 potently suppresses cytokine production by Toll-like receptors (TLRs) that signal through the adaptor MyD88 but is inactivated via caspase-8-mediated cleavage downstream of death receptors, TLR3, or TLR4. Here, we examined the mechanism whereby N4BP1 limits inflammatory responses. In macrophages, deletion of N4BP1 prolonged activation of inflammatory gene transcription at late time points after TRIF-independent TLR activation. Optimal suppression of inflammatory cytokines by N4BP1 depended on its ability to bind polyubiquitin chains, as macrophages and mice-bearing inactivating mutations in a ubiquitin-binding motif in N4BP1 displayed increased TLR-induced cytokine production. Deletion of the noncanonical IκB kinases (ncIKKs), Tbk1 and Ikke, or their adaptor Tank phenocopied N4bp1 deficiency and enhanced macrophage responses to TLR1/2, TLR7, or TLR9 stimulation. Mechanistically, N4BP1 acted in concert with the ncIKKs to limit the duration of canonical IκB kinase (IKKα/β) signaling. Thus, N4BP1 and the ncIKKs serve as an important checkpoint against over-exuberant innate immune responses.
    Keywords:  Toll-like receptors; cytokines; inflammation; innate immunity; signal transduction
    DOI:  https://doi.org/10.1016/j.immuni.2024.04.004
  6. mBio. 2024 May 03. e0052124
    Inhibitory mechanisms of decoy receptor 3 in cecal ligation and puncture-induced sepsis.
    Jingqian Su, Wenzhi Chen, Fen Zhou, Rui Li, Zhiyong Tong, Shun Wu, Zhen Ye, Yichao Zhang, Ben Lin, Xing Yu, Biyun Guan, Zhihua Feng, Kunsen Chen, Qi Chen, Long Chen.
      Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies.IMPORTANCE: Sepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.
    Keywords:  anti-inflammatory; decoy receptor 3; gut microbiota; sepsis
    DOI:  https://doi.org/10.1128/mbio.00521-24
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