Current topics in microbiology and immunology最新文献

{"title":"Disrupted Resolution Mechanisms in the Onset and Progression of Chronic Liver Disease.","authors":"Joan Clària, Berta Romero-Grimaldo, Bryan J Contreras, María Belén Sánchez-Rodríguez, Carlos Rojano, Esther Titos, Cristina López-Vicario","doi":"10.1007/82_2026_365","DOIUrl":"https://doi.org/10.1007/82_2026_365","url":null,"abstract":"<p><p>Disruption of physiological resolution mechanisms converts what should be a self-limiting inflammatory response into a persistent and pathogenic process. In the context of liver disease, when inflammation fails to resolve appropriately, it becomes chronic, driving ongoing tissue injury and repair responses that ultimately promote the development and progression of liver fibrosis. This defective resolution is also evident in the advanced stages of chronic liver disease, such as cirrhosis, where patients develop a state of immune dysfunction characterized by simultaneous systemic inflammation and impaired host defense responses. This dysfunctional immune state increases susceptibility to bacterial infections and contributes to the development of extrahepatic organ failure, which are major determinants of morbidity and mortality in these patients. This chapter reviews the current understanding of inflammation resolution across the spectrum of chronic liver disease. The wide clinical and pathological heterogeneity of these conditions, ranging from early and mild liver tissue injury to advanced cirrhosis and its complications, provides a unique framework to study the dynamics of inflammatory burden and its resolution.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149285838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specialized Pro-resolving Mediators and Mimetics: Bridging Resolution Biology and Therapeutic Development.","authors":"Braden Millar, Catherine Godson, Monica de Gaetano","doi":"10.1007/82_2026_367","DOIUrl":"https://doi.org/10.1007/82_2026_367","url":null,"abstract":"<p><p>Inflammation is a fundamental host defense mechanism that protects against infection and tissue injury. However, failure to appropriately resolve inflammation contributes to the pathogenesis of numerous pathologies. The discovery of endogenous mediators of inflammation resolution has changed our understanding of the dynamics of self-limiting inflammation. The active resolution of inflammation reflects tightly orchestrated responses to specific mediators including cytokines, peptides, and specialized pro-resolving mediators (SPMs), a superfamily of bioactive lipid mediators that includes the lipoxin, resolvin, protectin, and maresin families of SPMs. These mediators exert their potent pleiotropic immunoregulatory actions at nanomolar concentrations through mechanisms including activation of specific G-protein-coupled receptors (GPCRs), to regulate endothelial activation and promote the cessation of neutrophil recruitment, enhanced macrophage efferocytosis, removal of inflammatory debris, and restoration of tissue homeostasis. The lipoxins (LXs), arachidonate-derived mediators, were the first SPMs described and have emerged as attractive potential therapeutics for acute and chronic inflammatory diseases due to their broad anti-inflammatory and pro-resolving actions. However, translation of these bioactions has proven difficult as a result of their structural limitations and poor chemical stability, making them susceptible to metabolic inactivation. For this reason, the quest to develop structurally protected mimetics has recently gained momentum, and these analogs are designed to preserve receptor-mediated bioactivity while enhancing stability and efficacy. This chapter reviews the biosynthesis, biological functions, and receptor pharmacology of the major SPM families. Furthermore, the therapeutic potential of SPMs and their mimetics is analyzed, summarizing the rationale underpinning the design and preclinical testing of these therapeutic leads across a range of inflammatory and tissue injury models.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149285755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defective Inflammation Resolution in Cystic Fibrosis: Cellular Mechanisms and Emerging Pro-resolving Therapies in the CFTR Modulator Era.","authors":"Mario Romano, Simona D'Orazio, Domenico Mattoscio, Matteo Mucci, Roberto Plebani, Shameer Pillarisetti, Antonio Recchiuti","doi":"10.1007/82_2026_362","DOIUrl":"https://doi.org/10.1007/82_2026_362","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is a fatal monogenic hereditary disease that affects approximately 100,000 people worldwide. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, impairing biosynthesis and/or function of a protein that regulates chloride and bicarbonate fluxes. CFTR loss of function is associated with aberrant, non-resolving inflammation that in combination with recurrent infection leads to respiratory insufficiency. Cellular and molecular studies have uncovered failures in key mechanisms of inflammation resolution, consequent to loss of function of CFTR expressed by leukocytes, platelets, and epithelial and endothelial cells. This chapter illustrates these processes and discusses pro-resolving therapeutic approaches to combat CF inflammation.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"15-Hydroxyprostaglandin Dehydrogenase: A Key Metabolic Enzyme for Prostaglandins, 12-Hydroxyheptadecatrienoic Acid, and Resolvins.","authors":"Hsin-Hsiung Tai, Haining Zhu, Nan Chiang","doi":"10.1007/82_2026_360","DOIUrl":"https://doi.org/10.1007/82_2026_360","url":null,"abstract":"<p><p>The 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a key prostaglandin catabolic enzyme. It is well known that 15-PGDH catalyzes the oxidation of prostaglandin E₂ (PGE₂) to form 15-oxo-PGE₂ that is biologically inactive. The catalytic sites of 15-PGDH have been revealed using site-directed mutagenesis, homology modeling, molecular docking, and molecular dynamics simulation. 15-PGDH also catalyzes the oxidation of 12S-hydroxyheptadecatrienoic acid (12-HHT) to generate the 12-keto-heptadecatrienoic acid (12-KHT). Substrate specificity studies were carried out using a steady-state kinetic approach with highly purified 15-PGDH, and 12-HHT gave the highest affinity and efficiency among all 15-PGDH substrates including PGE₂ and PGF₂α. 12-HHT was shown to be a potent ligand for leukotriene B₄ receptor 2 (BLT2), and the 12-HHT-BLT2 axis is likely to play an important role in wound healing and tissue regeneration. Unlike 15-oxo-PGE₂, 12-KHT remains bioactive with an affinity to BLT2 comparable to that of 12-HHT. In addition to prostaglandins and 12-HHT, the pro-resolving mediators, including lipoxins and resolvins, are also sensitive to rapid inactivation via dehydrogenation by 15-PGDH. Screening of a list of natural products, anti-inflammatories and cardiovascular drugs, several 15-PGDH inhibitors have been identified, which have high potency in promoting wound healing and regeneration, likely via the preservation of the anti-inflammatory and pro-resolving substrates of 15-PGDH, including 12-HHT, lipoxins, and resolvins. The detailed studies on 15-PGDH substrate specificity provide molecular basis for designing longer-acting stable analogs of the substrates or high-affinity inhibitors that block 15-PGDH enzymatic activity. These stable analogs and inhibitors could have therapeutic potential in limiting inflammatory and neurodegenerative diseases, as well as stimulating wound healing and regeneration, leading to healthy aging.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolution Failure in Multiple Sclerosis: Linking Lipid Mediators to Neuroinflammation and Disease Progression.","authors":"Valerio Chiurchiù","doi":"10.1007/82_2026_357","DOIUrl":"https://doi.org/10.1007/82_2026_357","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic immune-mediated and neurodegenerative disorder of the central nervous system characterized by highly heterogeneous clinical courses and progressive accumulation of disability. Traditionally viewed as a relapsing inflammatory disease driven by peripheral autoimmunity, emerging evidence instead supports a continuum in which early immune attacks evolve into compartmentalized, chronic \"smoldering\" pathology that persists independently of overt relapses. This chapter integrates current knowledge of MS pathogenesis, focusing on the central emerging concept that MS reflects a fundamental failure of inflammation resolution. Specialized pro-resolving mediators (SPMs), which normally terminate inflammation and promote tissue repair, are consistently dysregulated in experimental and human MS. Preclinical studies demonstrate that SPMs such as resolvins, lipoxins, and maresins reduce neuroinflammation, prevent demyelination, and restore immune balance, while human metabolipidomic data reveal systemic deficiencies in pro-resolving lipid pathways alongside enrichment of pro-inflammatory eicosanoids. At the cellular level, SPMs modulate both innate and adaptive immune responses, stabilize blood-brain barrier integrity, and promote reparative phenotypes; however, reduced responsiveness in MS-derived cells suggests combined defects in mediator availability and signaling capacity.Collectively, these findings reposition MS as a disorder of defective resolution biology rather than solely excessive inflammation. This framework unifies relapsing and progressive disease mechanisms and provides a rationale for therapeutic strategies aimed at restoring endogenous resolution pathways. Nevertheless, key questions remain regarding the origin of resolution failure, its stage-specific dynamics, and the translational efficacy of SPM-based interventions in humans.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolution Medicine: Steps to Uncovering the Specialized Pro-resolving Mediator Superfamily and Their Potent Functions in Resolving Inflammation.","authors":"Charles Nicholas Serhan","doi":"10.1007/82_2026_354","DOIUrl":"https://doi.org/10.1007/82_2026_354","url":null,"abstract":"<p><p>Surgery, barrier breaks, injury, and microbial invasions initiate the cardinal signs of inflammation: heat, redness, swelling, and pain mediated by the classic prostaglandins. Tissue histology defined the acute inflammatory response, its initiation with leukocyte infiltration, and normally self-limited resolution phase. Resolution, once thought to be passive, is an active program accompanied by temporal biosynthesis of novel lipid mediators that activate clearance of apoptotic neutrophils (polymorphonuclear neutrophil-PMN) and cellular debris and limit the further PMN infiltration. Structural elucidation of these novel potent products demonstrated their biosynthesis from essential polyunsaturated fatty acids. The pro-resolving mediator superfamily includes lipoxins, resolvins, protectins, and maresins, which are each structurally distinct, their complete stereochemistry, biosynthesis, roles of epoxide intermediates, and potent functions all confirmed with total organic synthesis. Given their specialized new physiologic functions, they are grouped together based on this new function and termed the \"specialized pro-resolving mediator\" (SPM) superfamily. This chapter outlines, for the first time, the lines of reasoning and experimentation that led to SPM discovery and their physiologic functions along with evidence that establishes resolvin structures and biosynthesis which are conserved in evolution. Supplementation with omega-3 in humans increases SPMs. Leukocytes, muscle, and vagus nerve also produce SPMs. SPMs act on stem cells, are organ protective, and stimulate resolution by limiting the magnitude and duration of inflammation. SPMs reduce cancer burden, pain, neuroinflammation, and vascular inflammation. SPM mimetics demonstrate in pivotal human trials that activating endogenous resolution programs can control excessive and chronic inflammation. These results give a new platform for treating inflammation-associated diseases via resolution medicine.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolution Pathways in the Context of Viral Infections.","authors":"Filipe Resende, Vanessa Pinho, Lirlândia Pires Sousa, Vivian Vasconcelos Costa, Mauro Martins Teixeira","doi":"10.1007/82_2026_359","DOIUrl":"https://doi.org/10.1007/82_2026_359","url":null,"abstract":"<p><p>Inflammation is a central host response against viral infections. However, accumulating evidence indicates that when excessive, misdirected, or unresolved, the inflammatory response becomes a driver of disease, ultimately contributing to tissue damage, dysfunction, and death. The proper termination of inflammation relies on the timely engagement of resolution programs, and pro-resolving mediators have been extensively investigated in a variety of inflammatory settings. Although much is known in the context of bacterial infections, the role of resolution pathways in viral diseases remains relatively underexplored. Here, we summarize current evidence showing (1) that the levels of pro-resolving mediators are modulated during viral infections and are correlated with severe disease; (2) preclinical studies supporting their endogenous roles; and (3) the effects of the exogenous administration of mediators of inflammation resolution and their receptors during viral infection in humans and experimental models. We further discuss the capacity of viruses to hijack resolution pathways, as exemplified by the AnxA1/FPR2 axis during herpes simplex and influenza A virus infection. Finally, we propose that therapeutic strategies aimed at enhancing resolution may extend beyond the acute phase of infection, offering benefits in post-viral sequelae, including secondary bacterial infections and neurological complications, as observed in COVID-19 and arbovirus-associated disorders.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated Resolution of Inflammation in Atherosclerosis: Mechanistic Insights and Therapeutic Opportunities.","authors":"Manikandan Subramanian","doi":"10.1007/82_2026_361","DOIUrl":"https://doi.org/10.1007/82_2026_361","url":null,"abstract":"<p><p>Atherosclerosis is a chronic inflammatory disease of medium- and large-sized arteries and the underlying cause of most myocardial infarctions and strokes. It develops when circulating lipoproteins accumulate within the arterial intima, triggering recruitment of monocytes, neutrophils, and other immune cells that initiate and sustain vascular inflammation. Macrophages ingest modified lipids and become foam cells, while ongoing inflammatory signalling promotes cell death, extracellular matrix remodelling, and progressive plaque growth. In early lesions, macrophages efficiently remove apoptotic cells through efferocytosis, a process that prevents secondary necrosis and promotes anti-inflammatory and tissue repair pathways. However, in advanced plaques, this clearance pathway becomes defective, leading to the accumulation of apoptotic and necrotic debris, expansion of the necrotic core, and weakening of the fibrous cap-features associated with plaque instability, rupture, and thrombosis.Specialised pro-resolving mediators (SPMs), a class of bioactive lipid mediators derived from omega-3 fatty acids, play a critical role in orchestrating the resolution of inflammation. SPMs enhance macrophage efferocytosis, suppress pro-inflammatory signalling pathways, and promote tissue repair and vascular homeostasis. Importantly, advanced atherosclerotic plaques exhibit impaired SPM biosynthesis and an imbalance between pro-inflammatory and pro-resolving lipid mediators, contributing to persistent inflammation and defective clearance of dying cells.This chapter examines the interplay between vascular inflammation, impaired efferocytosis, and defective resolution pathways in atherosclerosis. It outlines the cellular and molecular mechanisms governing efferocytosis and SPM signalling and how these processes become disrupted during plaque progression. The chapter also reviews current therapeutic strategies aimed at restoring effective clearance and inflammation resolution, including SPM-based approaches and targeting efferocytosis pathways, and discusses emerging translational opportunities for stabilising atherosclerotic plaques and reducing cardiovascular risk.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stromal Niches Regulating Skin Immunity and Repair.","authors":"Bikram Dasgupta, Yuval Rinkevich","doi":"10.1007/82_2026_358","DOIUrl":"https://doi.org/10.1007/82_2026_358","url":null,"abstract":"<p><p>Fibroblasts are central architects of skin structure and repair, and their interactions with immune cells are essential for maintaining a normal healing trajectory. In this chapter, we discuss how fibroblasts arise from distinct developmental lineages with high regenerative potential, how they diversify across dermal layers in adulthood, and how these context-specific states shape wound outcomes. We outline the synchronized communication between fibroblast subsets, neutrophils, and macrophages driving controlled inflammation, organized matrix remodeling, and effective tissue restoration in acute injury. We contrast this with chronic wounds and fibro-proliferative disorders, where fibroblast-immune communication is altered, leading to persistent inflammation, excessive matrix deposition, or stalled repair. Together, these insights underscore fibroblast-immune crosstalk in regulating, maintaining, and subverting wound healing.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolving Cancer: Specialized Pro-resolving Mediators as Host-Directed Regulators of Tumor Progression and Therapy Response.","authors":"Molly M Gilligan, Dipak Panigrahy","doi":"10.1007/82_2026_356","DOIUrl":"https://doi.org/10.1007/82_2026_356","url":null,"abstract":"<p><p>Cancer is sustained not only by pro-inflammatory signaling but also by inadequate restoration of tissue homeostasis, e.g., failed or dysregulated resolution. Specialized pro-resolving mediators (SPMs) are enzymatically generated lipid autacoids that actively coordinate termination of inflammation, including limiting neutrophil influx, stimulating macrophage efferocytosis, counter-regulating inflammatory mediator production, and supporting tissue repair and regeneration. In oncology, these processes intersect with tumor progression, perioperative biology, treatment-induced cell death, immunotherapy responsiveness, and late metastatic recurrence. Since 2021, major advances have reframed how we view SPMs in the context of cancer: (i) efferocytosis has emerged as a central but paradoxical mechanism that can both suppress debris-driven inflammation and enable tumor immune escape; (ii) resolution-phase macrophage mediators have been reported to target dormant disseminated tumor cells and their fibrotic niche; (iii) resolution defects linked to impaired SPM biosynthesis (including ALOX15 loss) may explain inconsistent omega-3 prevention trials; (iv) neutrophil extracellular traps (NETs) have become a rapidly expanding interface between inflammation, therapy stress, and metastatic risk; and (v) mechanistic updates, including SPM receptor signaling models, have sharpened the need for rigorous, context-aware interpretation. This chapter focuses specifically on cancer biology and translation, positioning SPMs as unique host-directed modulators with attractive potential for therapeutic intervention in cancer treatment and cancer prevention. Rather than blocking inflammation, SPMs actively reprogram inflammatory responses to maintain tumor dormancy and precancer conditions. This distinction is particularly relevant in cancer, where chronic non-resolving inflammation arises not only from tumor biology itself but also from therapeutic interventions such as surgery, chemotherapy, cytotoxic and immune-targeting therapy, and radiation.</p>","PeriodicalId":11102,"journal":{"name":"Current topics in microbiology and immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}