bims-traimu Biomed News
on Trained immunity
Issue of 2026–01–18
twelve papers selected by
Yantong Wan, Southern Medical University
  1. Trained immunity in acute and chronic neurological diseases.
  2. Recent perspectives on macrophage memory: types, mechanisms, and characteristics in pulmonary diseases.
  3. Paclitaxel induces trained immunity via the GPR183-STING axis to enhance host defense against MRSA infection.
  4. [Role of Trained Immunity in the Association Between Periodontitis and Rheumatoid Arthritis].
  5. Injectable hydrogels for osteomyelitis treatment induce metabolic reprogramming for protection against reinfection.
  6. The "cytokine storm" in infection and sepsis: win the battle but lose the war.
  7. SENP6 Restrains NLRP3 Inflammasome Activation via DeSUMOylation-Driven K48-Linked Ubiquitination of NLRP3 in Acute Lung Injury.
  8. Inflammatory imbalance in ambulance patients is associated with sepsis and septic shock.
  9. Cytokine storm.
  10. EGFR orchestrates neutrophil activation and NETosis via CEBPβ-dependent PGLYRP1 induction.
  11. KIF13B Attenuates Sepsis-Induced Myocardial Dysfunction through the Stabilization of PLIN5.
  12. Lineage tracing reveals the origins and dynamics of macrophages in lung injury and repair.
  1. Elife. 2026 Jan 15. pii: e106037. [Epub ahead of print]15
    Trained immunity in acute and chronic neurological diseases.
    Sijia Zhang, Arthur Liesz.
      Trained immunity, the long-term reprogramming of innate immune cells to elicit an enhanced response upon subsequent challenges, has become a key concept in understanding a wide range of pathologies, including both acute and chronic inflammatory disorders. Recent evidence suggests that trained immunity also plays a significant role in the development and progression of various neurological disorders and related comorbidities, in which brain pathology can lead to trained immunity. This review summarizes the current understanding of trained immunity within both brain-resident immune cells and myeloid-derived innate immune cells, focusing on their roles in neurological disorders, such as ischemic brain injury, Parkinson's disease, and Alzheimer's disease. Additionally, we explore the heterogeneity of trained immunity across different conditions and its potential applications in clinical neurology.
    Keywords:  alzheimer's disease; brain disorders; immunology; inflammation; innate immunity; neuroscience; parkinson's disease; stroke; trained immunity
    DOI:  https://doi.org/10.7554/eLife.106037
  2. Cell Commun Signal. 2026 Jan 15.
    Recent perspectives on macrophage memory: types, mechanisms, and characteristics in pulmonary diseases.
    Shuyong Wang, Bin Wang, Yonghui Qiu, Yiwei Lu, Hongjun Gu, Bo Wang, Jiang Wang.
      
    Keywords:  Epigenetic reprogramming; Innate immune memory; Macrophages; Metabolic reprogramming; Pulmonary diseases; Tolerance; Trained immunity
    DOI:  https://doi.org/10.1186/s12964-026-02658-w
  3. Vet Res. 2026 Jan 16.
    Paclitaxel induces trained immunity via the GPR183-STING axis to enhance host defense against MRSA infection.
    Cheng-Kai Zhou, Jia-Bao Zhang, Yong-Jun Yang, Wei Chen, Zhen-Zhen Liu.
      Methicillin-resistant Staphylococcus aureus (MRSA) remains a major global health threat with limited prophylactic options. Trained immunity, characterized by nonspecific functional reprogramming of innate immune cells, offers a promising strategy for infection control. Here, we identify paclitaxel (PTX), a microtubule-stabilizing agent widely used in cancer therapy, as a novel inducer of trained immunity in macrophages. Unlike the microtubule-destabilizing agent nocodazole (Noco), PTX enhanced macrophage proinflammatory responses, phagocytosis, and bacterial killing upon secondary stimulation. Mechanistically, PTX-induced training activated the stimulator of interferon genes protein (STING) pathway, evidenced by increased phosphorylation of STING, TBK1, and IRF3. STING deficiency abolished the trained immune responses and antimicrobial functions. PTX also triggered metabolic reprogramming toward aerobic glycolysis via the Akt-mTOR-HIF1α pathway, which was essential for the trained phenotype. Transcriptomic and functional analyses further revealed that the GPR183-STING axis mediated PTX-induced trained immunity. Inhibition of GPR183 impaired STING activation and suppressed functional responses in vitro. In a murine MRSA pneumonia model, PTX-trained mice showed reduced bacterial burden, preserved lung barrier integrity, and enhanced immune activation, all of which were reversed by GPR183 inhibition or STING deficiency. Collectively, our findings uncover a previously unrecognized immunomodulatory function of PTX and highlight the therapeutic potential of targeting the GPR183-STING axis to enhance trained immunity against resistant bacterial infections.
    Keywords:  MRSA; Paclitaxel; infection prevention; macrophages; trained immunity
    DOI:  https://doi.org/10.1186/s13567-025-01704-8
  4. Sichuan Da Xue Xue Bao Yi Xue Ban. 2025 Nov 20. 56(6): 1709-1714
    [Role of Trained Immunity in the Association Between Periodontitis and Rheumatoid Arthritis].
    Renjing You, Yujia Cui, Jianxun Sun.
      Trained immunity is a state of enhanced immune responsiveness based on innate immune (epigenetic) memory. It has recently been reported that trained immunity plays an important role in the comorbidity of periodontitis and rheumatoid arthritis (RA). Epigenetic modifications in hematopoietic stem and progenitor cells (HSPCs) can activate trained immunity in bone marrow-derived cells, a mechanism closely associated with the onset and progression of periodontitis and other related systemic diseases. Exhibiting hyper-reactivity, trained immune cells are capable of migrating to distant joint sites and eliciting a more intense inflammatory response upon external stimulation. This review focuses on the underlying mechanisms of trained immunity and its involvement in both periodontitis and RA. Understanding the role of trained immunity in the association between periodontitis and RA provides valuable insights for further research and the development of therapeutic strategies for inflammatory comorbidities, such as periodontitis and RA.
    Keywords:  Periodontitis; Review; Rheumatoid arthritis; Trained immunity
    DOI:  https://doi.org/10.12182/20250960503
  5. Nat Commun. 2026 Jan 13.
    Injectable hydrogels for osteomyelitis treatment induce metabolic reprogramming for protection against reinfection.
    Haoyi Chen, Li Wei, Qiang Yu, Chenxi Wang, Huizhen Fan, Ming Li, Ruonan Dong, Yingying Ma, Jiahao Jiang, Lianfu Deng, Mei X Wu, Min Lu.
      Osteomyelitis, especially multidrug-resistant cases, remains a formidable clinical challenge due to recurrent infections and antibiotic limitations. Here, we present an injectable GaCuVan&HACHO-BSA hydrogel that self-assembles in situ within the bone marrow cavity-the epicenter of trained immunity-to simultaneously eradicate pathogens, induce innate immune memory, and regenerate bone. The hydrogel captured bacteria, virulence factors, and inflammatory mediators through multivalent interactions with enhanced injectability, biocompatibility, and sustained antigen release, making it ideal for minimally invasive treatment of osteomyelitis-related bone defects. Mechanistically, adsorbed pathogen signatures activated pattern recognition receptors, triggering metabolic reprogramming (elevated succinate/ATP/lactate), HIF-1α stabilization, amplified glycolysis and inflammation (COX2/iNOS/CD86), and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) production-collectively inducing trained immunity with cross-protection against homologous/heterologous reinfection. Furthermore, glycyrrhizic acid promoted bone tissue repair and modulated immune responses. By converging antimicrobial defense, innate immune memory, and tissue repair into a single platform, this work redefines osteomyelitis management and advances immunomodulatory biomaterials for clinical translation.
    DOI:  https://doi.org/10.1038/s41467-026-68318-2
  6. Mil Med Res. 2026 Jan 12. 12(1): 95
    The "cytokine storm" in infection and sepsis: win the battle but lose the war.
    Jiang-Bo Fan, Qin-Yuan Li, Xi-Feng Feng, Si-Yuan Huang, Rui Wang, Feng-Ying Liao, Di Liu, Wen-Yi Liu, Jian-Hui Sun, Hua-Cai Zhang, Hui-Ting Zhou, Jian-Xin Jiang, Zhen Wang, Ling Zeng.
      The cytokine storm, a life-threatening systemic inflammatory syndrome, is the primary driver of multiorgan failure in different clinical situations, including severe infections, autoimmune diseases, chimeric antigen receptor (CAR) T cell immunotherapy for cancer, and genetic syndromes. This review focuses primarily on cytokine storms triggered by severe infections such as viral pneumonia and bacterial sepsis, and explores the underlying mechanisms of cytokine storms and potential therapeutic interventions. Cytokine storms are characterized primarily by the excessive release of proinflammatory cytokines, which are triggered by pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and PANoptosis, all of which activate immune signaling cascades. Amplification mechanisms involve positive feedback loops and the failure of negative feedback mechanisms, leading to uncontrolled inflammation. Like a pyrrhic victory, the excessive activation of the immune system eliminated invading pathogens but caused catastrophic damage due to multiple organ dysfunction syndrome (MODS), turning the life-saving response into a life-threatening war. Therapeutic strategies, including cytokine antagonists, Janus kinase (JAK) inhibitors, caspase inhibitors, glucocorticoids, and blood purification therapies, aim to interrupt the self-amplifying cycle of inflammation that propagates organ injury, thereby reducing MODS and mortality. Challenges include optimizing the treatment timing and patient stratification. Future research should focus on combination therapies and personalized medicine based on the heterogeneity of infections and sepsis. Advances in multiomics and targeted therapies provide new hope for managing infections and sepsis.
    Keywords:  Cytokine storm; Inflammatory response; Multiple organ dysfunction syndrome; Sepsis; Severe infection
    DOI:  https://doi.org/10.1186/s40779-025-00678-0
  7. Research (Wash D C). 2026 ;9 1069
    SENP6 Restrains NLRP3 Inflammasome Activation via DeSUMOylation-Driven K48-Linked Ubiquitination of NLRP3 in Acute Lung Injury.
    Angran Gu, Bailun Wang, Yi Zhang, Chang Sun, Yi Wei, Jie Yan, Yizheng Yang, Yichen Wang, Runmeng Liu, Ruirui Zhang, Jifa Liu, Changping Gu, Yuelan Wang.
      The NLRP3 inflammasome is a pivotal component of the innate immune system, responding to infections and cellular damage. Its dysregulation has been implicated in numerous inflammatory diseases, although the mechanisms controlling its activation remain incompletely elucidated. Recent studies have highlighted the importance of posttranslational modifications, such as ubiquitination and SUMOylation, in regulating inflammasome activation. In this study, we demonstrate that SENP6, a SUMO-specific protease, negatively regulates NLRP3 inflammasome activation by promoting K48-linked polyubiquitination of NLRP3. SENP6-deficient macrophages exhibit enhanced NLRP3 activation and increased secretion of interleukin-1β (IL-1β) and IL-18, resulting in amplified inflammatory responses. Mechanistically, SENP6 interacts with NLRP3 and promotes its degradation through the autophagy-lysosomal pathway via K48-linked polyubiquitination. We further identified that SENP6 deSUMOylated NLRP3 at specific lysine residues (K23, K204, and K689), which was essential for maintaining NLRP3 stability. Additionally, SENP6 recruits the E3 ubiquitin ligase MARCHF7 to promote NLRP3 ubiquitination and subsequent degradation. In vivo, SENP6 deficiency exacerbates NLRP3 activation and lung inflammation in lipopolysaccharide-induced endotoxic shock-associated lung injury, and enhances inflammatory responses in alum-induced peritonitis. Our findings reveal a novel mechanism whereby SENP6 modulates NLRP3 inflammasome activation via SUMOylation, ubiquitination, and degradation, providing new insights into potential therapeutic strategies for inflammasome-related pathologies.
    DOI:  https://doi.org/10.34133/research.1069
  8. Cytokine. 2026 Jan 10. pii: S1043-4666(26)00002-5. [Epub ahead of print]199 157107
    Inflammatory imbalance in ambulance patients is associated with sepsis and septic shock.
    X-HiDE Consortium
      The host immune response in sepsis involves both pro- and anti-inflammatory mechanisms, with monocytes playing a central role in the process. We have previously identified an in vitro response profile of endotoxin (LPS) tolerant primary human monocytes, consisting of eight cytokines/chemokines as well as a set of five transcription factors. In the current study, we evaluated differences in expression levels of these investigated molecular markers across different patient groups (patients with or without infection, and with or without sepsis), and their association with clinical outcomes (septic shock and in-hospital mortality), among 809 ambulance patients. The results showed that patients with sepsis displayed the lowest HLA-DRA expression levels together with the lowest TNF/IL-10 ratio, while most other cytokine/chemokines and gene expressions were elevated. Higher levels of HGF, CCL8, CCL2, TNF and IL-10, as well as upregulation of HIF1A and NFKBIA were seen in septic patients with septic shock. The data suggests that the investigated immunological markers linked to immunosuppressed monocyte responses are associated with patients with sepsis and septic shock.
    Keywords:  Emergency medical services; Inflammation; Monocytes; Sepsis; Septic shock
    DOI:  https://doi.org/10.1016/j.cyto.2026.157107
  9. Nat Rev Dis Primers. 2026 Jan 15. 12(1): 1
    Cytokine storm.
    Rajendra Karki, Mihai G Netea, Caroline Diorio, Thirumala-Devi Kanneganti.
      Cytokine storm describes a spectrum of clinical manifestations that feature increased cytokine levels in circulation owing to overactivated immune responses. These increased concentrations of cytokines can cause tissue and organ damage, potentially leading to lethality. Cytokine storm can be induced by a variety of underlying clinical conditions, including infection, auto-inflammatory and autoimmune conditions, monogenic causes, or therapeutic intervention, which often makes diagnosis and treatment difficult. However, studies have identified conserved molecular mechanisms that inform therapeutic strategies. Cytokine storm is initiated by cytokine production and exacerbated by a self-amplifying positive feedback loop between cytokines and inflammatory cell death (PANoptosis). The process begins when cells detect triggers and undergo inflammatory signalling to produce and release cytokines via canonical secretion pathways or through lytic cell death such as pyroptosis and PANoptosis. This release of inflammatory cytokines, and potentially of other damage-associated molecules, can then drive inflammation and cell death in neighbouring cells through paracrine PANoptosis, resulting in further cytokine release and the amplification of the cycle. Improved understanding of the molecular and cellular mechanisms driving cytokine storm is critical for developing effective therapeutic strategies and improving clinical outcomes.
    DOI:  https://doi.org/10.1038/s41572-025-00677-4
  10. Cell Death Differ. 2026 Jan 15.
    EGFR orchestrates neutrophil activation and NETosis via CEBPβ-dependent PGLYRP1 induction.
    Xiaolei Liu, Yue Lu, Yuanbo Guo, Guorong Huang, Jiahui Li, Jingran Lin, Zhijie Li, Liangqing Zhang, Hanhui Zhong, Yiwen Zhang, Jing Tang.
      Excessive neutrophil activation and neutrophil extracellular trap (NET) release drive systemic inflammation and organ injury in sepsis, yet the upstream regulatory pathways remain incompletely defined. Here, we identify epidermal growth factor receptor (EGFR) as a critical neutrophil-intrinsic regulator of NETosis. EGFR expression was markedly elevated in neutrophils from patients with sepsis and correlated with disease severity. Neutrophil-specific EGFR deletion in mice improved survival after polymicrobial sepsis by reducing cytokine storm, tissue injury, and NET formation. Mechanistically, EGFR associated with CCAAT/enhancer-binding protein beta (CEBPβ) and recruited Mitogen-activated protein kinase 14 (MAPK14) to phosphorylate CEBPβ, promoting its nuclear localization and transcriptional activation of peptidoglycan recognition protein 1 (PGLYRP1). Elevated PGLYRP1, in turn, amplified NETs release via autocrine engagement of triggering receptor expressed on myeloid cell-1 (TREM-1), establishing a feed-forward inflammatory loop. Administration of recombinant PGLYRP1 or forced CEBPβ overexpression reversed the protection conferred by EGFR deficiency, confirming the centrality of this axis. These findings define an unrecognized EGFR-MAPK14-CEBPβ-PGLYRP1-TREM1 circuit that links receptor signaling to pathological NETosis and highlight a promising therapeutic target to attenuate neutrophil-driven immunopathology in sepsis.
    DOI:  https://doi.org/10.1038/s41418-026-01660-6
  11. Research (Wash D C). 2026 ;9 1033
    KIF13B Attenuates Sepsis-Induced Myocardial Dysfunction through the Stabilization of PLIN5.
    Lianxin Zhang, Guolin Miao, Si Mei, Yufei Han, Yitong Xu, Wenxi Zhang, Jingxuan Chen, Kaikai Lu, Yinqi Zhao, Zihao Zhou, Jinxuan Chen, Jiabao Guo, Pingping Lai, Sin Man Lam, Guanghou Shui, Ling Zhang, Weiguang Zhang, Wei Huang, Yuhui Wang, Xunde Xian.
      Sepsis-induced cardiac dysfunction (SICD) is a major contributor to mortality in sepsis. Kinesin family member 13B (KIF13B) has been identified as a critical protective factor for metabolic disorder and cardiovascular disease; however, the role of KIF13B in SICD remains unknown. After introducing lipopolysaccharide or cecal ligation and puncture surgery to wild-type (WT) and global Kif13b knockout (Kif13b -/-) mice combined with lipopolysaccharide-treated neonatal rat cardiomyocytes, we found that KIF13B expression levels were markedly down-regulated in septic hearts and cardiomyocytes. Kif13b deletion exacerbated SICD progress with reduced cardiac contractile function and resulted in increased mortality, accompanied by promoted lipid accumulation, fibrosis, and mitochondrial impairment. Mechanistically, the loss of KIF13B enhanced the lysosomal degradation of the lipid-droplet-associated protein perilipin 5 (PLIN5), thus disrupting the mitochondrial localization of PLIN5 and then impairing cardiac lipid homeostasis and proper mitochondrial function. Nevertheless, cardiac-directed AAV9-PLIN5 gene therapy sufficiently corrected cardiac dysfunction, inhibited lipid accumulation, and reduced oxidative stress in Kif13b -/- mice with SICD. In summary, these findings provide a new insight into the molecular mechanism underlying the pathogenesis of SICD, highlighting the KIF13B/PLIN5 axis as a potential therapeutic target for the treatment of SICD.
    DOI:  https://doi.org/10.34133/research.1033
  12. Cell Discov. 2026 Jan 14. 12(1): 3
    Lineage tracing reveals the origins and dynamics of macrophages in lung injury and repair.
    Hengwei Jin, Jialing Mou, Huan Zhu, Kuo Liu, Mingjun Zhang, Zhenqian Zhang, Stefan Pflanz, Karim Ei Kasmi, Zhaoyuan Liu, Florent Ginhoux, Kathy O Lui, Bin Zhou.
      Macrophages play a vital role in tissue repair and regeneration following injury. However, the cell fate, dynamic responses, and functions of macrophages from various origins during lung injury and repair are not fully understood. Here, we used genetic lineage tracing and scRNA-seq approaches to explore the temporal and spatial roles of tissue-resident and infiltrating macrophages during pulmonary fibrosis. We observed a sharp reduction in tissue-resident macrophages during the early inflammatory phase, with their numbers stabilizing during recovery. Monocytes contributed substantially to the macrophage population during the fibrotic phase, initially differentiating into interstitial macrophages and later transitioning into alveolar macrophages through a transient state. Genetic ablation of monocytes led to a reduction in the number of infiltrating macrophages and alleviated pulmonary fibrosis. Mechanistically, Notch signaling was negatively correlated with Wnt/β-catenin signaling in the regulation of monocyte recruitment and pulmonary fibrosis. Our study reveals the dynamic contributions and functions of macrophages from various sources in lung injury and regeneration.
    DOI:  https://doi.org/10.1038/s41421-025-00859-0
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