Journal of Innate Immunity最新文献

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5-Methoxytryptophan Protects against Toll-Like Receptor 2-Mediated Renal Tissue Inflammation and Fibrosis in a Murine Unilateral Ureteral Obstruction Model. 5-甲氧基色氨酸在小鼠单侧输尿管梗阻模型中对toll样受体2介导的肾组织炎症和纤维化具有保护作用。
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2025-01-07 DOI: 10.1159/000543275
Jing-Yiing Wu, Guan-Lin Lee, Yu-Fan Chueh, Cheng-Chin Kuo, Yu-Juei Hsu, Kenneth K Wu
{"title":"5-Methoxytryptophan Protects against Toll-Like Receptor 2-Mediated Renal Tissue Inflammation and Fibrosis in a Murine Unilateral Ureteral Obstruction Model.","authors":"Jing-Yiing Wu, Guan-Lin Lee, Yu-Fan Chueh, Cheng-Chin Kuo, Yu-Juei Hsu, Kenneth K Wu","doi":"10.1159/000543275","DOIUrl":"10.1159/000543275","url":null,"abstract":"<p><strong>Introduction: </strong>5-Methoxytryptophan (5-MTP) is a cellular metabolite with anti-inflammatory properties. Several recent reports indicate that 5-MTP protects against post-injury tissue fibrosis. It was unclear how 5-MTP controls tissue fibrosis. We postulated that 5-MTP attenuates renal interstitial fibrosis by blocking toll-like receptor 2 (TLR2) and transforming growth factor β (TGFβ) signaling pathways.</p><p><strong>Methods: </strong>In vivo experiments were carried out in a well-established unilateral ureteral obstruction (UUO) model in wild-type (WT) and tlr2-/- mice. The effect of 5-MTP on renal fibrosis was evaluated by pretreatment of WT UUO mice with intraperitoneal administration of 5-MTP. To determine whether 5-MTP attenuates fibrosis by inhibiting TLR2 and TGFβ signaling pathways, we evaluated the effect of 5-MTP on TLR2-induced fibroblast phenotypic switch in NRK-49F fibroblasts and TLR2 and TGFβ signaling pathways in human proximal tubular epithelial cells (HPTECs) and RAW264.7 macrophages stimulated with Pam3CSK4 (Pam3) or TGFβ1.</p><p><strong>Results: </strong>UUO-induced renal fibrosis was abrogated in tlr2-/- mice consistent with a crucial role of TLR2 in UUO-induced renal fibrosis. UUO-induced macrophage infiltration and pro-fibrotic cytokine production in renal tissues were suppressed by tlr2 knockout. 5-MTP administration attenuated renal tissue fibrosis accompanied by reduction of macrophage infiltration and IL-6 and TGFβ levels. 5-MTP inhibits TLR2 upregulation and blocks TLR2-MyD88-TRAF6 signaling pathway in macrophages. Furthermore, 5-MTP blocked Pam3- and TGFβ1-induced phenotypic switch of NRK-49F to myofibroblasts and inhibited Pam3- and TGFβ1-induced signaling pathways in HPTECs and RAW264.7 cells.</p><p><strong>Conclusion: </strong>5-MTP is effective in protecting against UUO-induced renal interstitial fibrosis by blocking TLR2 and TGFβ signaling pathways.</p><p><strong>Introduction: </strong>5-Methoxytryptophan (5-MTP) is a cellular metabolite with anti-inflammatory properties. Several recent reports indicate that 5-MTP protects against post-injury tissue fibrosis. It was unclear how 5-MTP controls tissue fibrosis. We postulated that 5-MTP attenuates renal interstitial fibrosis by blocking toll-like receptor 2 (TLR2) and transforming growth factor β (TGFβ) signaling pathways.</p><p><strong>Methods: </strong>In vivo experiments were carried out in a well-established unilateral ureteral obstruction (UUO) model in wild-type (WT) and tlr2-/- mice. The effect of 5-MTP on renal fibrosis was evaluated by pretreatment of WT UUO mice with intraperitoneal administration of 5-MTP. To determine whether 5-MTP attenuates fibrosis by inhibiting TLR2 and TGFβ signaling pathways, we evaluated the effect of 5-MTP on TLR2-induced fibroblast phenotypic switch in NRK-49F fibroblasts and TLR2 and TGFβ signaling pathways in human proximal tubular epithelial cells (HPTECs) and RAW264.7 macrophages stimulated with Pam3CSK4 (","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"78-94"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Patients Hospitalized with COVID-19 Demonstrate Distinct Plasma Cytokine and Chemokine Concentrations in vivo and TLR-Mediated Cytokine and Chemokine Production in Whole Blood in vitro. COVID-19住院患者体内血浆细胞因子和趋化因子浓度不同,tlr介导的体外全血细胞因子和趋化因子产生不同。
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2025-05-28 DOI: 10.1159/000545432
Athena N Nguyen, Thomas S Kouyate, Kevin Ryff, Alec L Plotkin, Simon Doss-Gollin, Sanya Thomas, Kerry McEnaney, Al Ozonoff, Joann Diray-Arce, Ofer Levy, Oludare A Odumade, Lindsey R Baden, Simon D van Haren, Kinga K Smolen
{"title":"Patients Hospitalized with COVID-19 Demonstrate Distinct Plasma Cytokine and Chemokine Concentrations in vivo and TLR-Mediated Cytokine and Chemokine Production in Whole Blood in vitro.","authors":"Athena N Nguyen, Thomas S Kouyate, Kevin Ryff, Alec L Plotkin, Simon Doss-Gollin, Sanya Thomas, Kerry McEnaney, Al Ozonoff, Joann Diray-Arce, Ofer Levy, Oludare A Odumade, Lindsey R Baden, Simon D van Haren, Kinga K Smolen","doi":"10.1159/000545432","DOIUrl":"10.1159/000545432","url":null,"abstract":"<p><strong>Introduction: </strong>SARS-CoV-2's continued global health impact underscores the importance of ongoing pathogenesis research. Insights into the host's first line of defense against severe COVID-19 identify actionable biomarkers, informing disease management or therapeutics. Yet, the innate immune response, including cytokines, chemokines, adenosine deaminases (ADAs) and Toll-like receptors (TLRs), relevant to COVID-19 remain incompletely characterized.</p><p><strong>Methods: </strong>Peripheral blood was longitudinally collected between May 2020 and March 2021 from COVID-19 hospitalized adults (N = 79) and healthy controls (HCs) (N = 14; not tested, assumed COVID-negative, no viral exposure or symptoms). Heparinized blood was fractionated for plasma cryopreservation and in vitro whole blood TLR-stimulation employing TLR-3, -4, and -7/8 agonists. Post-stimulation culture supernatants were analyzed using multiplex and enzymatic assays.</p><p><strong>Results: </strong>Upon hospitalization, plasma concentrations of IFNγ, IL-6, CXCL10, and ADAs were significantly upregulated compared to convalescent time points and HCs. Participants with fatal COVID-19 exhibited higher IL-27, CXCL10, and ADAs concentrations upon admission. Plasma cytokines, chemokines, and ADAs were positively correlated and associated with distinct temporal patterns. TLR-stimulated cell cultures from patients produced reduced IFNα2, IFNγ, IL-12p40, and IL-12p70 compared to HCs or later time points.</p><p><strong>Conclusion: </strong>Higher plasma concentrations of IL-27, CXCL10, and ADAs at admission were associated with severe COVID-19 and mortality. Reduced TLR-mediated IFNα2, IFNγ, and IL-12p70 production suggests COVID dampens Th1-polarizing innate immune responses, providing insight into immunological sequelae of SARS-CoV-2 infection.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"288-301"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the Role of Macrophages and Their Associated Structures in Rheumatoid Arthritis. 探讨巨噬细胞及其相关结构在类风湿关节炎中的作用。
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2025-02-12 DOI: 10.1159/000543444
Xin Tian, Jingjing Chen, Yujie Hong, Yang Cao, Jing Xiao, Yan Zhu
{"title":"Exploring the Role of Macrophages and Their Associated Structures in Rheumatoid Arthritis.","authors":"Xin Tian, Jingjing Chen, Yujie Hong, Yang Cao, Jing Xiao, Yan Zhu","doi":"10.1159/000543444","DOIUrl":"10.1159/000543444","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rheumatoid arthritis (RA) is a chronic, invasive autoimmune disease characterized by symmetrical polyarthritis involving synovial inflammation. Epidemiological studies indicate that the incidence of RA continues to rise, yet the pathogenesis of this disease remains not fully understood. A significant infiltration of macrophages is observed in the synovium of RA patients. It can be inferred that macrophages likely play a crucial role in the onset and progression of RA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;This review aims to summarize the research progress on the mechanisms by which macrophages and their associated structures contribute to RA, as well as potential therapeutic approaches, aiming to provide new insights into the study of RA pathogenesis and its clinical treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key messages: &lt;/strong&gt;During the course of RA, besides the inherent roles of macrophages, these cells respond to microenvironmental changes such as pathogen invasion or tissue damage by undergoing polarization, pyroptosis, or forming macrophage extracellular traps (METs), all of which influence inflammatory responses and immune homeostasis, thereby mediating the occurrence and development of RA. Additionally, macrophages secrete exosomes, which participate in intercellular communication and signal transduction processes, thus contributing to the progression of RA. Therefore, it is critical to elucidate how macrophages and their related structures function in RA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rheumatoid arthritis (RA) is a chronic, invasive autoimmune disease characterized by symmetrical polyarthritis involving synovial inflammation. Epidemiological studies indicate that the incidence of RA continues to rise, yet the pathogenesis of this disease remains not fully understood. A significant infiltration of macrophages is observed in the synovium of RA patients. It can be inferred that macrophages likely play a crucial role in the onset and progression of RA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;This review aims to summarize the research progress on the mechanisms by which macrophages and their associated structures contribute to RA, as well as potential therapeutic approaches, aiming to provide new insights into the study of RA pathogenesis and its clinical treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key messages: &lt;/strong&gt;During the course of RA, besides the inherent roles of macrophages, these cells respond to microenvironmental changes such as pathogen invasion or tissue damage by undergoing polarization, pyroptosis, or forming macrophage extracellular traps (METs), all of which influence inflammatory responses and immune homeostasis, thereby mediating the occurrence and development of RA. Additionally, macrophages secrete exosomes, which participate in intercellular communication and signal transduction processes, thus contributing to the progression of RA. Therefore, it is critical to elucidate how macrophages and their related structures function ","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"17 1","pages":"95-111"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11820663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Liver X Receptors and Inflammatory-Induced C/EBPβ Selectively Cooperate to Control CD38 Transcription. 肝脏X受体和炎症诱导的C/EBPb选择性合作控制CD38转录。
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2024-12-19 DOI: 10.1159/000543274
Estibaliz Glaría, Pol Rodríguez Martínez, Joan Font-Díaz, Juan Vladimir De la Rosa, Antonio Castrillo, Dylan J Crawshaw, Jose Manuel Vidal Taboada, Josep Saura, Jonathan Matalonga, Eduardo Nunes Chini, Carme Caelles, Annabel F Valledor
{"title":"Liver X Receptors and Inflammatory-Induced C/EBPβ Selectively Cooperate to Control CD38 Transcription.","authors":"Estibaliz Glaría, Pol Rodríguez Martínez, Joan Font-Díaz, Juan Vladimir De la Rosa, Antonio Castrillo, Dylan J Crawshaw, Jose Manuel Vidal Taboada, Josep Saura, Jonathan Matalonga, Eduardo Nunes Chini, Carme Caelles, Annabel F Valledor","doi":"10.1159/000543274","DOIUrl":"10.1159/000543274","url":null,"abstract":"<p><strong>Introduction: </strong>Macrophages abundantly express liver X receptors (LXRs), which are ligand-dependent transcription factors and sensors of several cholesterol metabolites. In response to agonists, LXRs promote the expression of key lipid homeostasis regulators. Cross talk between LXRs and inflammatory signals exists in a cell type- and gene-specific manner. A common feature in the macrophage response to inflammatory mediators is the induction of CCAAT/enhancer-binding protein beta (C/EBPβ), a master transcriptional regulator and lineage-determining transcription factor in monocytes/macrophages.</p><p><strong>Methods: </strong>Quantitative real-time PCR in control and C/EBPβ-deficient macrophages was used to explore the role of C/EBPβ in the cross talk between inflammatory mediators and the macrophage response to pharmacological LXR activation. The functional interaction between C/EBPβ and LXRs on selected genomic regions was further characterized by chromatin-immunoprecipitation (ChIP) and gene reporter studies.</p><p><strong>Results: </strong>Whereas inflammatory signaling repressed several LXR-regulated genes involved in lipid metabolism, these effects were conserved after deletion of C/EBPβ. In contrast, inflammatory mediators and LXRs synergistically induced the expression of the multifunctional protein CD38 in a C/EBPβ-dependent manner. C/EBPβ and LXRs bound to several regions with enhancer activity upstream and within the mouse Cd38 gene and their functional cooperation in macrophages required intact binding sites for LXR and C/EBPβ.</p><p><strong>Conclusion: </strong>This study reveals positive cross talk between C/EBPβ and LXRs during the macrophage inflammatory response, which selectively impacts CD38 expression.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"56-77"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human Blood Non-Classical/Classical Monocyte Cells Are Heterogeneously Presented in Severe COVID-19 and Correlate with Disease Activity. 在严重的 COVID-19 中,人体血液中的 NC/CL 细胞呈现异质性,并与疾病活动相关。
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2024-11-25 DOI: 10.1159/000542652
Danhong Zhou, Yu Shen, Suxian Jing, Dong Qiu, Yang Wang, Qiuxia Qu, Cheng Chen
{"title":"Human Blood Non-Classical/Classical Monocyte Cells Are Heterogeneously Presented in Severe COVID-19 and Correlate with Disease Activity.","authors":"Danhong Zhou, Yu Shen, Suxian Jing, Dong Qiu, Yang Wang, Qiuxia Qu, Cheng Chen","doi":"10.1159/000542652","DOIUrl":"10.1159/000542652","url":null,"abstract":"<p><strong>Introduction: </strong>COVID-19 is highly heterogeneous, ranging from cases with mild disease with an almost asymptomatic carrier to severe cases, in which the disease evolves rapidly. A better understanding of monocyte response during SARS-CoV-2 infection would highlight potential biomarkers and establish other possible approaches for severe cases.</p><p><strong>Methods: </strong>The study group consisted of 32 COVID-19 patients and 18 health controls from June 2023 to March 2024. The COVID-19 patients were further classified as mild and severe illnesses based on World Health Organization (WHO) criteria. For flow cytometric analysis, 50 µL of peripheral blood and 1 µL of specific monoclonal antibodies were added to each cytometric tube for surface marker detection.</p><p><strong>Results: </strong>Here, the promising finding was that the blood non-classical/classical monocyte (NC/CL) subset was skewed toward NChighCLlow and NClowCLhigh clusters among the severe COVID-19 patients. The NChighCLlow cluster in severe COVID-19 displayed a distinct clinical phenotype, implying a higher 7-day disease progression rate (p = 0.019) and a worse 28-day survival (p = 0.026). Moreover, the secretion of IL-1β and IFN-γ was primarily attributed to CL subset in monocytes, while IL-6 was secreted mainly by NC subset.</p><p><strong>Conclusion: </strong>As supported, regarding cytokine profile in context of SARS-CoV-2 infection, it was identified that circulating NC cells are proinflammatory cells most related to regulatory cells, while CL subset displayed an effective capacity to virus. These findings have implications toward optimizing evaluation in severe COVID-19, and developing strategies that target altered balance of NC/CL cell subsets.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"1-9"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family. 染色体1q31.3区域内的常见单倍型决定了整个补体因子H蛋白家族的系统浓度。
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2025-03-26 DOI: 10.1159/000545342
Bert R J Veuskens, Mara van Rossum, Emi Cattenstart, Mieke C Brouwer, Gerard van Mierlo, Judy Geissler, Karin van Leeuwen, Jin Liu, Robert A Anstadt, Burt T Richards, Gregory S Hageman, Taco W Kuijpers, Erik J M Toonen, Richard B Pouw
{"title":"Common Haplotypes within the Chromosome 1q31.3 Region Determine Systemic Concentrations of the Entire Complement Factor H Protein Family.","authors":"Bert R J Veuskens, Mara van Rossum, Emi Cattenstart, Mieke C Brouwer, Gerard van Mierlo, Judy Geissler, Karin van Leeuwen, Jin Liu, Robert A Anstadt, Burt T Richards, Gregory S Hageman, Taco W Kuijpers, Erik J M Toonen, Richard B Pouw","doi":"10.1159/000545342","DOIUrl":"10.1159/000545342","url":null,"abstract":"<p><strong>Introduction: </strong>The alternative pathway of complement activation is consistently active, keeping the complement system primed for immediate response. This constant \"tick-over\" mechanism is regulated by the factor H (FH) protein family, which encompasses seven highly related proteins: FH, FHL-1, and five FH-related (FHR-1 to -5) proteins. The current model is that the FHRs compete with FH and FHL-1 to fine-tune their activities. Genetic studies of this complex locus have revealed distinct haplotypes associating with a wide array of human diseases, underscoring its significant role in complement regulation. Nevertheless, a comprehensive analysis of systemic concentrations of all FH protein family members, accounting for known genetic variability within the population, is still lacking.</p><p><strong>Methods: </strong>Systemic levels of each member of the FH protein family were quantified with the use of recently developed target specific ELISAs. Next, a genetic analysis focused on the chromosome 1q31.3 region was performed using next generation sequencing and multiplex ligase probe-dependent amplification.</p><p><strong>Results: </strong>We report systemic protein levels of each member of the FH protein family found in vivo and demonstrate common haplotypes within the CFH locus give rise to classifiable protein expression patterns, establishing distinct ratios between FH, FHL-1, and the FHRs.</p><p><strong>Conclusions: </strong>The established reference intervals and identified genetic effects provide a benchmark for further research and emphasize the importance of including all family members when studying their role in both health and disease.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"244-261"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interactions of Probiotics with the Immune Cells of Patients with COVID-19 Pneumonia. 益生菌与COVID-19肺炎患者免疫细胞的相互作用
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2025-05-27 DOI: 10.1159/000545873
Ioannis Mitrou, George Dimopoulos, Konstantina Dakou, Panagiotis Koufargyris, Georgia Damoraki, Theologia Gkavogianni, Evangelos J Giamarellos-Bourboulis
{"title":"Interactions of Probiotics with the Immune Cells of Patients with COVID-19 Pneumonia.","authors":"Ioannis Mitrou, George Dimopoulos, Konstantina Dakou, Panagiotis Koufargyris, Georgia Damoraki, Theologia Gkavogianni, Evangelos J Giamarellos-Bourboulis","doi":"10.1159/000545873","DOIUrl":"10.1159/000545873","url":null,"abstract":"<p><strong>Introduction: </strong>In severe COVID-19, excessive cytokine release may be driven by SARS-CoV-2. We investigated the modulatory effect of probiotics taking into consideration direct interaction with the immune gut cells.</p><p><strong>Methods: </strong>Fifty-five patients with confirmed COVID-19 infection were classified by the presence of acute respiratory distress syndrome (ARDS) or not. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with lipopolysaccharide (LPS), a preparation of four probiotics (LactoLevure® containing Saccharomyces boulardii, Bifidobacterium lactis BB-12, Lactobacillus acidophilus LA-5, and L. plantarum) and/or recombinant human interferon-gamma (rhIFNγ) and tocilizumab. Cytokine concentrations were measured in cell supernatants. Gene expression of Toll-like receptors 2 (TLR2) and 4 (TLR4) was performed by quantitative real-time polymerase chain reaction (RT-PCR). Results were associated with the level of viremia.</p><p><strong>Results: </strong>Probiotics decreased tumor necrosis factor-alpha (TNFα) production by the PBMCs of both ARDS and non-ARDS patients. LPS stimulated the production of interleukin (IL)-1β, IL-6 in non-ARDS patients. IL-6 production was maintained in the presence of probiotics. rhIFNγ enhanced LPS-stimulated cytokine production by PBMCs; this was not the case when PBMCs were stimulated by probiotics. Probiotics upregulated TLR2 and LPS downregulated TLR4 in the PBMCs of patients with ARDS. PBMCs from patients with viremia had more cytokine production by probiotic stimulation.</p><p><strong>Conclusion: </strong>Probiotics interact with the immune system of COVID-19 patients by modulating the production of TNFα, IL-1β, and IL-6 in an IFNγ-independent mechanism.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":"17 1","pages":"277-286"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TLR2 or TLR4 Stimulation Induces Transmembrane TNF-Driven Priming in Macrophages Which Results in Improved Clearance of a Subsequent Staphylococcus aureus Infection. TLR2或TLR4刺激诱导巨噬细胞中跨膜(tm) tnf驱动的启动,从而改善后续金黄色葡萄球菌感染的清除。
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2025-05-28 DOI: 10.1159/000546011
Abby M Luu, Alexis A Hatton, Jasper Gattiker, Kelly M Shepardson, Monica N Hall, Evelyn Benson, Diane Bimczok, Agnieszka Rynda-Apple
{"title":"TLR2 or TLR4 Stimulation Induces Transmembrane TNF-Driven Priming in Macrophages Which Results in Improved Clearance of a Subsequent Staphylococcus aureus Infection.","authors":"Abby M Luu, Alexis A Hatton, Jasper Gattiker, Kelly M Shepardson, Monica N Hall, Evelyn Benson, Diane Bimczok, Agnieszka Rynda-Apple","doi":"10.1159/000546011","DOIUrl":"10.1159/000546011","url":null,"abstract":"<p><strong>Introduction: </strong>Toll-like receptor (TLR) engagement on macrophages can improve responsiveness to infection. TNF is upregulated following TLR2 or TLR4 stimulation. We sought to determine whether and how the two bioactive forms of TNF, soluble (sTNF) and transmembrane (tmTNF), may be contributing to macrophage priming, which improved responsiveness to subsequent Staphylococcus aureus infection.</p><p><strong>Methods: </strong>RNA sequencing and cytokine quantification assays identified differentially upregulated cytokines in response to TLR2 stimulation. Immortalized and primary bone marrow-derived macrophages (BMDMs) coupled with receptor blocking and cytokine supplementation were used to investigate whether/how prior TLR-primed macrophages improved S. aureus clearance.</p><p><strong>Results: </strong>TLR2 or TLR4 stimulated TNF-/- BMDMs failed to efficiently clear a subsequent S. aureus infection compared to TLR-stimulated wild-type (WT) BMDMs. Depletion of sTNF from TLR-stimulated WT BMDMs retained their improved S. aureus clearance. Exogenous sTNF supplementation to TNF-/- BMDMs did not rescue improved S. aureus clearance. Cell density assays showed cell-to-cell contact was important for TLR-induced improvement of S. aureus clearance. Conversely, blocking TNFR2 reduced BMDM clearance of S. aureus, despite TLR2 stimulation.</p><p><strong>Conclusions: </strong>Our results demonstrated that TNF produced in response to TLR stimulated BMDMs was required for improved clearance of a subsequent S. aureus infection. We found that sTNF did not contribute to this priming, which suggested that tmTNF may be critical for BMDM priming which leads to improved S. aureus clearance.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"302-319"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Streptococcus pyogenes Activates Human Platelets via Streptolysin S-Mediated Calcium Ion Influx. 化脓性链球菌通过溶血素s介导的钙离子内流激活人血小板。
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2025-03-03 DOI: 10.1159/000544951
Anna Riegner, Kristin Jahn, Jan Wesche, Thomas Thiele, Nikolai Siemens
{"title":"Streptococcus pyogenes Activates Human Platelets via Streptolysin S-Mediated Calcium Ion Influx.","authors":"Anna Riegner, Kristin Jahn, Jan Wesche, Thomas Thiele, Nikolai Siemens","doi":"10.1159/000544951","DOIUrl":"10.1159/000544951","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Streptococcus pyogenes (group A streptococcus, GAS) is an exclusively human pathogen. It causes a wide spectrum of diseases, ranging from mild infections such as pharyngitis to severe life-threatening conditions such as streptococcal toxic shock syndrome (STSS). Thrombocytopenia is a common feature of STSS and is associated with severe outcome. GAS produce a plethora of virulence factors, including streptolysin S (SLS), which has lytic as well as immunomodulatory properties. However, its role in platelet activation remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Washed human platelets were infected with GAS wild-type and SLS-deficient mutant (ΔsagA) strains. Platelet activation was assessed by measuring degranulation (CD62P expression). The role of calcium influx and the involvement of purinergic type 2 receptors (P2R) in platelet activation by GAS were assessed using chemical antagonists and calcium chelators.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;GAS activate human platelets via SLS-mediated calcium influx, marked by increased surface expression of CD62P. IVIG treatment improved platelet viability in wild-type infections but failed to prevent SLS-mediated activation. Blocking of P2 receptors via suramin or NF449 as well as the use of calcium chelators reduced SLS-mediated platelet activation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study identified SLS as an M-protein and consequently a serotype-independent activator of human platelets. While IVIG partially improved platelet viability in GAS infections, its inability to prevent excessive platelet activation underscores the need for additional treatment options in severe GAS infections.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Streptococcus pyogenes (group A streptococcus, GAS) is an exclusively human pathogen. It causes a wide spectrum of diseases, ranging from mild infections such as pharyngitis to severe life-threatening conditions such as streptococcal toxic shock syndrome (STSS). Thrombocytopenia is a common feature of STSS and is associated with severe outcome. GAS produce a plethora of virulence factors, including streptolysin S (SLS), which has lytic as well as immunomodulatory properties. However, its role in platelet activation remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Washed human platelets were infected with GAS wild-type and SLS-deficient mutant (ΔsagA) strains. Platelet activation was assessed by measuring degranulation (CD62P expression). The role of calcium influx and the involvement of purinergic type 2 receptors (P2R) in platelet activation by GAS were assessed using chemical antagonists and calcium chelators.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;GAS activate human platelets via SLS-mediated calcium influx, marked by increased surface expression of CD62P. IVIG treatment improved platelet viability in wild-type infections but failed to prevent SLS-mediated activation. Blocking of P2 receptors via suramin or NF449 as well as the use of calcium chelators","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"198-210"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11952823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Macrophage Evolution during Progression of Hepatitis Virus B-Related Acute-on-Chronic Liver Failure. 乙型肝炎病毒相关急性和慢性肝衰竭进展过程中的巨噬细胞进化
IF 4.7 3区 医学
Journal of Innate Immunity Pub Date : 2025-01-01 Epub Date: 2024-12-05 DOI: 10.1159/000542946
Jiawei Rao, Dongmei Ye, Ao Ren, Wenjin He, Xuzhi Zhang, Pengrui Chen, Qian Jian, Zongli Fu, Ronghai Deng, Yixin Hu, Yifang Gao, Yi Ma
{"title":"Macrophage Evolution during Progression of Hepatitis Virus B-Related Acute-on-Chronic Liver Failure.","authors":"Jiawei Rao, Dongmei Ye, Ao Ren, Wenjin He, Xuzhi Zhang, Pengrui Chen, Qian Jian, Zongli Fu, Ronghai Deng, Yixin Hu, Yifang Gao, Yi Ma","doi":"10.1159/000542946","DOIUrl":"10.1159/000542946","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatitis B virus (HBV)-related liver diseases, including hepatitis, cirrhosis, and liver failure, seriously threaten human lives and health worldwide. Innate and adaptive immune cells are all thought to participate in HBV-related diseases. However, there is a lack of information on the comprehensive landscape of the immune microenvironment.</p><p><strong>Methods: </strong>In this study, single-cell ribonucleic acid sequencing was performed on liver samples obtained from patients diagnosed with hepatitis, cirrhosis, and acute-on-chronic liver failure, which were caused by HBV. Trajectory analysis was performed to analyze the evolution of cell subsets, and branch expression analysis modeling was applied to visualize the changes in gene expression during evolution.</p><p><strong>Results: </strong>Finally, there was a significant increase in adaptive immune cells in the hepatitis and cirrhosis groups, whereas more innate immune cells were observed in the liver failure group. Furthermore, we found that monocytes underwent remarkable transcriptomic changes into FABP5+ macrophages, promoting the degranulation and chemotaxis of neutrophils through RESISTIN signaling, and LGMN+ macrophages, with the sequential activation of antigen presentation and defense to pathogens through SPP1 signaling.</p><p><strong>Conclusion: </strong>Macrophages were revealed as central to the progression of acute-on-chronic liver failure as they regulated the activation or inhibition of other immune cells, which could help in developing an effective novel therapy.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"29-43"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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