bims-traimu Biomed News
on Trained immunity
Issue of 2026–09–27
ten papers selected by
Yantong Wan, Southern Medical University
  1. Erratum for the Research Article "Systemically inducing trained immunity overcomes solid tumors' immunosuppressive microenvironment" by B. Priem et al.
  2. Trained Immunity in Childhood Vaccination.
  3. Paratuberculosis vaccination induces a phenotype consistent with trained immunity in bovine neutrophils.
  4. Extracellular vesicles redefine immune modulation through Toll-like receptor networks.
  5. Rationale for a live-attenuated vaccine for cryptosporidiosis.
  6. Attenuated Salmonella as a modulator of the cancer-immunity cycle: from innate activation to adaptive antitumor memory.
  7. Long-term reprogramming of classical monocytes with altered ontogeny mediates enhanced lung injury in sepsis survivors.
  8. Switching of transcriptional control from interferon regulatory factor 2 to interferon regulatory factor 1 drives innate immune cell activation.
  9. Inflammatory memory inactivates AMPK-stimulated DDR1 degradation to enable pancreatic cancer growth.
  10. Metastasis enables immunogenicity through migrasome-mediated antigen release.
  1. Sci Adv. 2026 Sep 25. 12(39): eaem0051
    Erratum for the Research Article "Systemically inducing trained immunity overcomes solid tumors' immunosuppressive microenvironment" by B. Priem et al.
      
    DOI:  https://doi.org/10.1126/sciadv.aem0051
  2. Acta Paediatr. 2026 Sep 22.
    Trained Immunity in Childhood Vaccination.
    ChenRongRong Cai, Lubnaa Hossenbaccus, Eva Kaufmann.
      Conventionally, vaccine design has focused on identifying antigens that induce durable T and B cell memory and provide long term protection against subsequent encounters with the same pathogen. Unconventionally, a growing number of epidemiological, preclinical, and clinical studies demonstrate that live vaccines, including Bacillus Calmette Guérin (BCG), measles-containing vaccines, and oral polio vaccine, induce protection through trained immunity, a form of metabolically and epigenetically mediated memory in innate immune cells and their progenitors. This concept is particularly relevant during early life, when adaptive immune responses are constrained and innate immunity represents the principal line of host defence. In this review, we discuss the unique characteristics of neonatal and infant immunity, summarize current evidence for trained immunity induced by childhood vaccines, and describe the bidirectional interplay between innate and adaptive immune memory. We further highlight the potential of trained immunity to broaden protection against severe infections, improve vaccine efficacy, and provide therapeutic opportunities for non-infectious paediatric diseases, including cancer and allergic disorders. Harnessing trained immunity represents a conceptual shift in paediatric vaccinology and may guide the development of next generation vaccines that provide broader and more resilient protection during the period of greatest immunological vulnerability.
    Keywords:  childhood; trained immunity; vaccination
    DOI:  https://doi.org/10.1111/apa.70751
  3. NPJ Vaccines. 2026 Aug 19. pii: 181. [Epub ahead of print]11(1):
    Paratuberculosis vaccination induces a phenotype consistent with trained immunity in bovine neutrophils.
    M Mugica-Unamuno, E Molina, M Oyanguren, P Mendívil, M Fernández, M V Geijo, R Arrazuria, J M Garrido, N Elguezabal.
      Vaccination decreases bacterial shedding and reduces the incidence and severity of infection by Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of paratuberculosis (PTB), a chronic granulomatous enteritis that economically impacts the dairy industry. An inactivated Map vaccine exhibits features suggestive of trained immunity in cattle, along with enhanced neutrophil (PMN) activation in rabbits. Although PMNs from healthy cattle exhibit antimicrobial effects against Map, the impact of vaccination on bovine PMN function remains undetermined. This study has further explored the mechanisms of trained immunity mediated by PMNs elicited by this vaccine in calves. PMN mediated phagocytosis, ROS production and NET release showed a significant increase in vaccinated calves upon stimulation in ex vivo assays. Furthermore, PMNs from vaccinated animals exhibited decreased motility that was partially restored upon ex vivo stimulation with Map. Upregulation of phagocytosis receptors such as TREM2 and PBDL1, genes related to NETosis TREM2, LYZ and F13A1 and downregulation of genes involved in chemotaxis, adhesion, and motility in vaccinated animals support these findings. Altogether, the data indicate that this inactivated Map vaccine induces changes consistent with trained immunity in calves.
    DOI:  https://doi.org/10.1038/s41541-026-01556-z
  4. Expert Opin Ther Targets. 2026 Sep 23.
    Extracellular vesicles redefine immune modulation through Toll-like receptor networks.
    Diana Romenskaja-Avgul, Augustas Pivoriunas.
       INTRODUCTION: Extracellular vesicles (EVs) are potent immunomodulators that can promote the transition from pro-inflammatory to regulatory immune responses across diverse pathological conditions. Tissue injury increases the release of damage- and pathogen-associated molecular patterns (DAMPs and PAMPs), which activate Toll-like receptors (TLRs) to rapidly initiate inflammatory and antiviral responses. Here, we propose that TLR signaling serves as a central axis through which EVs exert both pathogenic and therapeutic effects.
    AREAS COVERED: This review summarizes current evidence on EV crosstalk with surface and endosomal TLRs and discusses how these interactions may drive long-term reprogramming of target cells. We highlight lipid raft signaling as a unifying mechanism linking TLRs and other receptors to signaling hubs controlling pro- and anti-inflammatory responses. Finally, we propose a model in which EVs act as inducers of trained immunity in immunocompetent cells.
    EXPERT OPINION: EVs have emerged as key immunomodulators that transport diverse DAMPs, transmit danger signals to surrounding tissues, and may establish trained immunity, priming cells for subsequent insults. Conversely, therapeutic EVs can target hyperinflammatory cells by modulating aberrant TLR signaling and reprogramming them toward a restorative, pro-resolving phenotype.
    Keywords:  Extracellular vesicles; Toll-like receptors; lipid rafts; trained immunity
    DOI:  https://doi.org/10.1080/14728222.2026.2738343
  5. J Infect Dis. 2026 Sep 23. pii: jiag471. [Epub ahead of print]
    Rationale for a live-attenuated vaccine for cryptosporidiosis.
    A Clinton White, Sara M Dann, Alejandro Castellanos-Gonzalez.
      Natural Cryptosporidium infection causes development of protective immunity. Live-attenuated vaccines stimulate both adaptive and "trained" innate immune responses. With advances in parasite genetics, target identification, and in vitro cultivation, we now propose development of a live-attenuated vaccine for cryptosporidiosis.
    Keywords:  Cryptosporidium; cryptosporidiosis; live-attenuated; trained immunity; vaccination; vaccine
    DOI:  https://doi.org/10.1093/infdis/jiag471
  6. Front Immunol. 2026 ;17 1916229
    Attenuated Salmonella as a modulator of the cancer-immunity cycle: from innate activation to adaptive antitumor memory.
    Sofía Chilibroste, José Alejandro Chabalgoity, María Moreno, Amy Mónaco.
      Attenuated engineered strains of Salmonella have emerged as promising tools in cancer immunotherapy due to their intrinsic tumor-targeting properties and their ability to reshape the tumor immune microenvironment. Beyond their direct cytotoxic effects on tumor cells, Salmonella profoundly modulates both innate and adaptive immune responses, impacting multiple steps of the cancer-immunity cycle. In this review, we discuss how attenuated Salmonella induces immunogenic tumor cell death, promotes antigen release and cross-presentation, enhances lymphocyte activation, and facilitates immune cell infiltration into the tumor microenvironment. We also address its role in controlling metastatic disease and the induction of long-term adaptive immune memory. Furthermore, we highlight unresolved questions regarding the contribution of immune activation, tolerance, and trained immunity, which may underlie the transient nature of antitumor effects observed in some models. Finally, we examine the translational hurdles that have limited clinical efficacy-such as the balance between attenuation and potency, endotoxin tolerance, and preexisting immunity-and outline emerging engineering strategies to overcome them. Understanding these mechanisms is essential for optimizing Salmonella-based strategies and their integration with current immunotherapies.
    Keywords:  antitumor response; bacterial therapy; cancer immunotherapy; cancer-immune cycle; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2026.1916229
  7. JCI Insight. 2026 Sep 24. pii: e198551. [Epub ahead of print]
    Long-term reprogramming of classical monocytes with altered ontogeny mediates enhanced lung injury in sepsis survivors.
    Scott J Denstaedt, Breanna McBean, Alan P Boyle, Brett C Arenberg, Matthias Mack, Bethany B Moore, Michael W Newstead, Yamei Deng, Alexey I Nesvizhskii, Benjamin H Singer, Jennifer Cano, Hallie C Prescott, Helen S Goodridge, Rachel L Zemans.
      Patients who survive sepsis are predisposed to new hospitalizations for respiratory failure, but the underlying mechanisms are unknown. Using a murine model in which prior sepsis predisposes to enhanced lung injury, we previously discovered that classical monocytes persist in the lungs after long-term recovery from sepsis and exhibit enhanced cytokine expression after secondary challenge with intra-nasal lipopolysaccharide. Here, we hypothesized that immune reprogramming of post-sepsis monocytes and altered ontogeny predispose to enhanced lung injury. Monocyte depletion and/or adoptive transfer was performed three weeks and three months after sepsis. Monocytes from post-sepsis mice were necessary and sufficient for enhanced LPS-induced lung injury and promoted neutrophil degranulation. Prior sepsis enhanced JAK-STAT signaling and AP-1 accessibility in monocytes and shifted monocytes toward the neutrophil-like monocyte lineage. Neutrophil-like monocytes demonstrated a pro-inflammatory phenotype with enhanced IL-1β expression and reduced phagocytic capacity. In human sepsis and/or pneumonia survivors, monocytes were predictive of 90-day mortality and exhibit transcriptional and proteomic neutrophil-like signatures. We conclude that sepsis reprograms monocytes into a pro-inflammatory phenotype and skews bone marrow progenitors and monocytes toward the neutrophil-like lineage, predisposing them to induce neutrophil degranulation and lung injury.
    Keywords:  Epigenetics; Immunology; Infectious disease; Innate immunity; Monocytes; Pulmonology
    DOI:  https://doi.org/10.1172/jci.insight.198551
  8. Cell. 2026 Sep 22. pii: S0092-8674(26)01022-6. [Epub ahead of print]
    Switching of transcriptional control from interferon regulatory factor 2 to interferon regulatory factor 1 drives innate immune cell activation.
    Cristhian Cadena, Rohit Reja, Emma Bolech, Joshua D Webster, Vasumathi Kameswaran, Marco de Simone, Cynthia Chen, Jian Jiang, Kathy Hotzel, Christopher Bjornson, Kamela Alegre, Zhenyu Tan, Heidi J Elsaesser, Raymond Newland, Ryan Kelly, Spyros Darmanis, Bence Daniel, David G Brooks, Ishan Deshpande, Kim Newton, Nobuhiko Kayagaki, Vishva M Dixit.
      Interferon regulatory factor 2 (IRF2) is a transcription factor that prevents skin inflammation in mice and humans but, paradoxically, promotes pyroptosis by upregulating gasdermin D. How IRF2 activates some proinflammatory genes but suppresses inflammation is unclear. We show that skin inflammation in Irf2-deficient mice is driven by IRF1 activation of interferon-stimulated genes (ISGs). Chromatin profiling reveals that IRF1 and IRF2 occupy the same ISG regulatory sites, but as a weaker transcriptional activator, IRF2 limits ISG transcription by IRF1. Toll-like receptor (TLR) signaling favors IRF1-driven transcription by inducing Irf1. In addition, IRF1 recruits the ubiquitin ligase SPOP to ISG sites, resulting in proteasomal degradation of IRF2. This shift from IRF2 to IRF1 occupancy enhances ISG transcription. Collectively, these findings define a hierarchical transcriptional circuit in which IRF2 limits IRF1 activity under homeostatic conditions but is displaced during an immune response, allowing IRF1-dependent gene programs central to innate immunity and autoinflammation.
    Keywords:  IRF1; IRF2; ISGs; SPOP; Toll-like receptor
    DOI:  https://doi.org/10.1016/j.cell.2026.08.049
  9. Proc Natl Acad Sci U S A. 2026 Sep 29. 123(39): e2616901123
    Inflammatory memory inactivates AMPK-stimulated DDR1 degradation to enable pancreatic cancer growth.
    Fei Yang, Bo Lin, Yongkang Yuan, Zihang Yuan, Xiaohong Pu, Chunlan Wang, Da Zhang, Yang Yang, Kosuke Watari, Rongkui Luo, Jian Zhou, Xinrong Yang, Beicheng Sun, Michael Karin, Hua Su.
      Inflammation and stromal remodeling control pancreatic ductal adenocarcinoma (PDAC), but whether and how these cues are integrated at the molecular level remains unclear. Here, we identify a metabolic checkpoint that controls the stability of the collagen receptor discoidin domain receptor 1 (DDR1), and subsequent tumorigenesis. Defective Col-I remodeling deprives PDAC cells of the high-affinity DDR1 ligand, the ¾Col-I fragment, resulting in reduced cellular adenosine triphosphate (ATP) and activation of adenosine monophosphate-activated protein kinase (AMPK). AMPK phosphorylates DDR1 at T519, promoting its recognition by the E3 ubiquitin ligase adaptor FBXW2 and subsequent proteasomal degradation. Importantly, this degradation pathway can be disabled by inflammatory signals. Exposure to inflammatory cytokines induces methylation-dependent silencing of FBXW2, establishing an inflammatory memory that preserves DDR1 stability, enabling sustained ligand-triggered receptor oligomerization and downstream NF-κB-NRF2 signaling even in PDAC restrictive stromal environments. Together, these findings identify regulated receptor turnover as a mechanism through which stromal architecture, metabolic state, and inflammatory memory are integrated to control PDAC progression.
    Keywords:  DNA methylation; collagen cleavage; inflammatory memory; pancreatic cancer; receptor protein stability
    DOI:  https://doi.org/10.1073/pnas.2616901123
  10. Nat Immunol. 2026 Sep 22.
    Metastasis enables immunogenicity through migrasome-mediated antigen release.
    Dong Jiang, Jinzhao He, Renxiang Xie, Minghui Shi, Siyuan Liu, Haohao Jia, Bingjie Yang, Xiaojie Ruan, Xiaoyu Tao, Yuhan Xiang, Yining Chen, Lin Jiao, Xiaoyu Feng, Li Yu.
      Antigen release is a critical step in initiating antitumor immune responses, yet its regulation during metastasis is not well understood. Here we show that circulating tumor cells undergoing vascular migration produce migrasomes that serve as a metastasis-specific mechanism of antigen release. These migrasomes are enriched in tumor-associated antigens, including cancer-testis and mutated antigens, and are captured efficiently by antigen-presenting cells in secondary lymphoid organs, where they undergo cross-presentation to elicit CD8+ T cell-mediated immune responses that constrain metastatic progression. Genetic inhibition of migrasome formation enhances metastasis, while administration of purified cancer-derived migrasomes restores immune-mediated suppression of metastatic growth. These findings show paradoxically that metastasis can enhance tumor immunogenicity through migrasome-mediated antigen release, highlighting a link between cancer dissemination and immune activation and establishing migrasomes as a distinct and potent platform for endogenous tumor antigen delivery.
    DOI:  https://doi.org/10.1038/s41590-026-02641-0
This page is being maintained by Thomas Krichel. It was last updated on 2026‒09‒27 at 11:35.