bims-traimu 2025-05-25 papers

Issue of 2025–05–25
five papers selected by
Yantong Wan, Southern Medical University

Int J Biol Macromol. 2025 May 15. pii: S0141-8130(25)04731-2. [Epub ahead of print] 144179

Trained immunity driven by Enterococcus faecalis ribosomal protein S11 enhances antigen presentation and boosts influenza vaccine efficacy via nanoparticle delivery.

Jian-Gang Zhang, Cheng-Kai Zhou, Yu Gao, Xiao-Mei Zhang, Ke Ma, Zi-Ran Peng, Xue-Yue Luo, Zhen-Zhen Liu, Xiao-Qi Lin, Wei Chen, Yong-Jun Yang.

The limited availability of adjuvants poses a significant challenge in modern vaccine development, as they play a crucial role in enhancing vaccine efficacy. Trained immunity, driven by metabolic and epigenetic reprogramming of innate immune cells, offers a novel platform for adjuvant discovery. However, current studies predominantly focus on classical inducers such as β-glucan and BCG, limiting the exploration of key genes underlying trained immune responses. Here, we introduce a phenotypic evaluation model using Galleria mellonella larvae, identifying the gut commensal Enterococcus faecalis as a potent inducer of trained immunity. Through bioactivity-guided fractionation, we identified ribosomal protein S11 (RPS11) as the active agonist. Mechanistically, RPS11 induces trained immunity through TLR4-TET2 signaling-mediated ribosomal biogenesis inhibition, thereby shaping the enhanced MHC molecule expression phenotype in trained antigen-presenting cells. Notably, RPS11 conjugated with superparamagnetic iron oxide nanoparticles (RSNPs) significantly boosted the efficacy of an influenza vaccine. These findings highlight that harnessing the synergistic effects of innate and adaptive immune memory, combined with nanoparticle-based delivery of trained immunity agonists, presents a promising strategy for advancing next-generation vaccines against infectious diseases.

Keywords: Bioactivity-guided fractionation; Commensal bacteria; Nanoparticle vaccines; Ribosomal biogenesis; Trained immunity

DOI: https://doi.org/10.1016/j.ijbiomac.2025.144179

Fish Shellfish Immunol. 2025 May 20. pii: S1050-4648(25)00318-3. [Epub ahead of print]163 110429

Characterization of type 2 interleukin-1 receptor (IL-1R2) as an inhibitory regulator of trained immunity in teleost.

Shu Cui, Qiuxi Yang, Yuanxing Zhang, Qin Liu, Dahai Yang, Zhuang Wang.

Trained immunity refers to the immune memory of innate immune cells, which is driven by metabolic rewiring and epigenetic reprogramming after initial stimulation. Several endogenous inducers of trained immunity have been reported, such as oxidized low-density lipoprotein (oxLDL), interleukin, and interferon. However, the negative regulatory molecules of trained immunity remain largely elusive. In this study, we identify a member of IL-1 family receptors, interleukin-1 receptor 2 (IL-1R2), as a potential inhibitory regulator of trained immunity in turbot. Pre-incubating recombinant IL-1R2 protein (rIL-1R2) with turbot neutrophils could inhibit β-glucan-induced training phenotypes. Specifically, rIL-1R2 incubation significantly decreases the expression of genes involved in the TLR/IL-1R and downstream MAPK/NF-κB signaling pathway in trained neutrophils, and further reversing the elevated expression of pro-inflammatory cytokines such as IL-6 and TNF-α in response to bacterial reinfection. Moreover, rIL-1R2 inhibits the increasing production of intracellular reactive oxygen (ROS), myeloperoxidase (MPO) activity and neutrophil extracellular traps (NETs) in trained neutrophils, ultimately impairing the bacterial killing ability. Taken together, our work demonstrates that the decoy receptor IL-1R2 could negatively regulate trained immunity activation in turbot neutrophils. These findings enrich the theory of trained immunity in teleost fish and provide a potential target for disease prevention and treatment in aquaculture.

Keywords: Bactericidal activity; IL-1R2; Neutrophils; Trained immunity; Turbot

DOI: https://doi.org/10.1016/j.fsi.2025.110429

PLoS One. 2025 ;20(5): e0323376

β-glucan induced trained immunity enhances antibody levels in a vaccination model in mice.

Jainu Ajit, Qing Chen, Trevor Ung, Matthew Rosenberger, Jeremiah Kim, Ani Solanki, Jingjing Shen, Aaron P Esser Kahn.

Trained immunity improves disease resistance by strengthening our first line of defense, the innate immune system. Innate immune cells, predominantly macrophages, are epigenetically and metabolically rewired by β-glucan, a fungal cell wall component, to induce trained immunity. These trained macrophages exhibit increased co-stimulatory marker expression and altered cytokine production. Signaling changes from antigen-presenting cells, including macrophages, polarize T-cell responses. Recent work has shown that trained immunity can generally enhance protection against infection, and some work has shown increased protection with specific vaccines. It has been hypothesized that the trained cells themselves potentially modulate adaptive immunity in the context of vaccines. However, the mechanistic link between trained immunity and subsequent vaccinations to enhance antibody levels has not yet been identified. We report that trained immunity induced by a single dose of β-glucan increased antigen presentation in bone-marrow-derived macrophages (BMDMs) and CD4+ T cell proliferation in-vitro. Mice trained with a single dose of β-glucan a week before vaccination elicited higher antigen-specific antibody levels than untrained mice. Further experiments validate that macrophages mediate this increase. This effect persisted even after vaccinations with 100 times less antigen in trained mice. We report β-glucan training as a novel prophylactic method to enhance the effect of subsequent vaccines.

DOI: https://doi.org/10.1371/journal.pone.0323376

Neurosci Biobehav Rev. 2025 May 14. pii: S0149-7634(25)00206-4. [Epub ahead of print]174 106206

A restarted life: Resetting microglia innate immune memory.

Fangyuan Cheng, Bo Yan, Fanglian Chen, Ping Lei.

Microglia can achieve depletion and repopulation through various mechanisms, improving outcomes in multiple CNS diseases. Innate immune memory in microglia can undergo continuous reprogramming through epigenetics, facilitating iterative memory upgrades. Here, through a comprehensive literature review, we propose the concepts of the microglial innate immune memory prototype (MIIMP) and microglial temporally phased innate immune memory reset (MTPIIMR). The temporally phased innate immune memory are reflected not only in the formation of immune response prototypes in microglia but also in the partial reset of innate immune memory during the depletion and repopulation process. In the duel against time, single cycles of depletion and repopulation can yield benefits through partial innate immune memory reset, while multiple cycles accelerate microglial aging. Identifying the optimal solution to replace microglia for filling ecological niches and executing their functions perfectly is a formidable yet profoundly significant challenge.

Keywords: CSF1R inhibitor; Innate immune memory; Microgia; Repopulation

DOI: https://doi.org/10.1016/j.neubiorev.2025.106206

Immunology. 2025 May 21.

BCG Vaccination Reprograms the Function of M-MDSCs and Aggravates Necrotizing Enterocolitis in Neonates.

Yingying Chen, Hui Li, Yongmei Zhang, Fajie Zhao, Jie Zhou.

Bacillus Calmette-Guérin (BCG), a live-attenuated vaccine primarily used against tuberculosis (TB), also provides protection against a broad array of antigens or heterologous antigens through the induction of trained immunity (TI). While BCG is generally safe for full-term infants, its application in preterm infants is contentious due to their immature immune systems and heightened susceptibility to adverse effects. Preterm infants, particularly those with low birth weight, are at an elevated risk of severe complications, such as necrotizing enterocolitis (NEC), a life-threatening inflammatory condition of the intestines. NEC is characterised by dysregulated immune responses to microbial colonisation, with myeloid-derived suppressor cells (MDSCs) playing a crucial role in maintaining immune tolerance during early life. This study reveals that BCG vaccination significantly exacerbates NEC severity (p = 0.0048) by enhancing glycolysis and upregulating mTOR-HIF1α signalling in neonatal monocytic MDSCs (M-MDSCs), thereby impairing their immunosuppressive function. Pharmacological or genetic inhibition of mTOR-HIF1α signalling or glycolysis pathways restored M-MDSC function and mitigated NEC severity. These findings complement our previous work on BCG's effects on polymorphonuclear (PMN)-MDSCs and highlight the dual role of BCG: while it provides protective benefits in certain contexts, it may also increase NEC risk in preterm infants by disrupting MDSC-mediated immune tolerance. This study offers critical insights into the mechanisms underlying BCG's off-target effects and underscores the necessity of tailored vaccination strategies for preterm infants to minimise potential risks.

Keywords: bacillus Calmette–Guérin; glycolysis; mTOR‐HIF1α signalling; monocytic myeloid‐derived suppressor cells; necrotizing enterocolitis; rapamycin

DOI: https://doi.org/10.1111/imm.13946