Journal of Innate Immunity最新文献_第3页

Metabolism Shapes Immune Responses to Staphylococcus aureus. 代谢影响对金黄色葡萄球菌的免疫反应。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2023-11-28 DOI: 10.1159/000535482

Prabhakar Arumugam, Tammy Kielian

{"title":"Metabolism Shapes Immune Responses to Staphylococcus aureus.","authors":"Prabhakar Arumugam, Tammy Kielian","doi":"10.1159/000535482","DOIUrl":"10.1159/000535482","url":null,"abstract":"Background: Staphylococcus aureus (S. aureus) is a common cause of hospital- and community-acquired infections that can result in various clinical manifestations ranging from mild to severe disease. The bacterium utilizes different combinations of virulence factors and biofilm formation to establish a successful infection, and the emergence of methicillin- and vancomycin-resistant strains introduces additional challenges for infection management and treatment.Summary: Metabolic programming of immune cells regulates the balance of energy requirements for activation and dictates pro- versus anti-inflammatory function. Recent investigations into metabolic adaptations of leukocytes and S. aureus during infection indicate that metabolic crosstalk plays a crucial role in pathogenesis. Furthermore, S. aureus can modify its metabolic profile to fit an array of niches for commensal or invasive growth.Key messages: Here we focus on the current understanding of immunometabolism during S. aureus infection and explore how metabolic crosstalk between the host and S. aureus influences disease outcome. We also discuss how key metabolic pathways influence leukocyte responses to other bacterial pathogens when information for S. aureus is not available. A better understanding of how S. aureus and leukocytes adapt their metabolic profiles in distinct tissue niches may reveal novel therapeutic targets to prevent or control invasive infections.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10766399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451589","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

Mechanisms and Therapeutic Strategies for MAFLD Targeting TLR4 Signaling Pathways. 针对 TLR4 信号通路的 MAFLD 机制和治疗策略。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2023-12-21 DOI: 10.1159/000535524

Guanghui Ren, Changchuan Bai, Sitong Yi, Qingwei Cong, Ying Zhu

{"title":"Mechanisms and Therapeutic Strategies for MAFLD Targeting TLR4 Signaling Pathways.","authors":"Guanghui Ren, Changchuan Bai, Sitong Yi, Qingwei Cong, Ying Zhu","doi":"10.1159/000535524","DOIUrl":"10.1159/000535524","url":null,"abstract":"Background: Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases. The underlying pathophysiological mechanisms are intricate and involve various factors. Unfortunately, there is currently a lack of available effective treatment options. Toll-like receptors (TLRs) are a group of pattern-recognition receptors that are responsible for activating the innate immune system. Research has demonstrated that TLR4 plays a pivotal role in the progression of MAFLD by facilitating the pathophysiological mechanisms.Summary: Lipid peroxidation, pro-inflammatory factors, insulin resistance (IR), and dysbiosis of intestinal microbiota are considered as the pathogenic mechanisms of MAFLD. This review summarizes the impact of TLR4 signaling pathways on the progression of MAFLD, specifically in relation to lipid metabolic disorders, IR, oxidative stress, and gut microbiota disorders. Additionally, we emphasize the potential therapeutic approaches for MAFLD that target TLR4 signaling pathways, including the use of plant extracts, traditional Chinese medicines, probiotics, pharmaceuticals such as peroxisome proliferator-activated receptor antagonists and farnesol X agonists, and lifestyle modifications such as dietary changes and exercise also considered. Furthermore, TLR4 signaling pathways have also been linked to the lean MAFLD.Key messages: TLR4 plays a crucial role in MAFLD by triggering IR, buildup of lipids, imbalance in gut microbiota, oxidative stress, and initiation of immune responses. The mitigation of MAFLD can be accomplished by suppressing the TLR4 signaling pathway. In the future, it could potentially emerge as a therapeutic target for the condition.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10783892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830134","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

Impact of Extreme Prematurity, Chorioamnionitis, and Sepsis on Neonatal Monocyte Characteristics and Functions. 极度早产、绒毛膜羊膜炎和败血症对新生儿单核细胞特征和功能的影响。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-09-14 DOI: 10.1159/000541468

Khaleda Rahman Qazi, Dhanapal Govindaraj, Magalí Martí, Ymke de Jong, Georg Bach Jensen, Thomas Abrahamsson, Maria C Jenmalm, Eva Sverremark-Ekström

{"title":"Impact of Extreme Prematurity, Chorioamnionitis, and Sepsis on Neonatal Monocyte Characteristics and Functions.","authors":"Khaleda Rahman Qazi, Dhanapal Govindaraj, Magalí Martí, Ymke de Jong, Georg Bach Jensen, Thomas Abrahamsson, Maria C Jenmalm, Eva Sverremark-Ekström","doi":"10.1159/000541468","DOIUrl":"10.1159/000541468","url":null,"abstract":"Introduction: The innate branch of the immune system is important in early life, in particular for infants born preterm.Methods: We performed a longitudinal analysis of the peripheral monocyte compartment in extremely preterm children from a randomized, placebo-controlled study of probiotic supplementation. PBMCs and fecal samples were collected at several timepoints during the first months of life. Monocyte characteristics were analyzed by flow cytometry, and LPS-stimulated PBMC culture supernatants were analyzed by Luminex or ELISA. Plasma cytokines and gut microbiota composition were analyzed by ELISA and 16S rRNA-sequencing, respectively.Results: The extremely preterm infants had persistent alterations in their monocyte characteristics that were further aggravated in chorioamnionitis cases. They showed a markedly reduced TLR4 expression and hampered LPS-stimulated cytokine responses 14 days after birth. Notably, at later timepoints, TLR4 expression and LPS responses no longer correlated. Sepsis during the first weeks of life strongly associated with increased pro-inflammatory, and reduced IL-10, responses also at postmenstrual week 36. Further, we report a correlation between gut microbiota features and monocyte phenotype and responses, but also that probiotic supplementation associated with distinct monocyte phenotypic characteristics, without significantly influencing their responsiveness.Conclusion: Extremely preterm infants have monocyte characteristics and functional features that deviate from infants born full-term. Some of these differences persist until they reach an age corresponding to full-term, potentially making them more vulnerable to microbial exposures during the first months of life.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289291","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

Immunometabolites Direct the Pathogenesis of Bacterial Infection. 免疫代谢物引导着细菌感染的发病机制。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-07-01 DOI: 10.1159/000540093

Alice Prince

引用次数: 0

Pattern-Recognition Receptors and Immunometabolic Reprogramming: What We Know and What to Explore. 模式识别受体与免疫代谢重编程：我们的认知与探索。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-05-13 DOI: 10.1159/000539278

Vijay Kumar, John H Stewart Iv

{"title":"Pattern-Recognition Receptors and Immunometabolic Reprogramming: What We Know and What to Explore.","authors":"Vijay Kumar, John H Stewart Iv","doi":"10.1159/000539278","DOIUrl":"10.1159/000539278","url":null,"abstract":"Background: Evolutionarily, immune response is a complex mechanism that protects the host from internal and external threats. Pattern-recognition receptors (PRRs) recognize MAMPs, PAMPs, and DAMPs to initiate a protective pro-inflammatory immune response. PRRs are expressed on the cell membranes by TLR1, 2, 4, and 6 and in the cytosolic organelles by TLR3, 7, 8, and 9, NLRs, ALRs, and cGLRs. We know their downstream signaling pathways controlling immunoregulatory and pro-inflammatory immune response. However, the impact of PRRs on metabolic control of immune cells to control their pro- and anti-inflammatory activity has not been discussed extensively.Summary: Immune cell metabolism or immunometabolism critically determines immune cells' pro-inflammatory phenotype and function. The current article discusses immunometabolic reprogramming (IR) upon activation of different PRRs, such as TLRs, NLRs, cGLRs, and RLRs. The duration and type of PRR activated, species studied, and location of immune cells to specific organ are critical factors to determine the IR-induced immune response.Key message: The work herein describes IR upon TLR, NLR, cGLR, and RLR activation. Understanding IR upon activating different PRRs is critical for designing better immune cell-specific immunotherapeutics and immunomodulators targeting inflammation and inflammatory diseases.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916636","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

Development of a C3 Humanized Rat as a New Model for Evaluating Novel C3 Inhibitors. C3人源化大鼠作为评价新型C3抑制剂的新模型的建立。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2023-11-30 DOI: 10.1159/000534963

Jin Y Chen, Lingjun Zhang, Maojing Yang, Elizabeth D Hughes, Zachary T Freeman, Thomas L Saunders, Feng Lin

{"title":"Development of a C3 Humanized Rat as a New Model for Evaluating Novel C3 Inhibitors.","authors":"Jin Y Chen, Lingjun Zhang, Maojing Yang, Elizabeth D Hughes, Zachary T Freeman, Thomas L Saunders, Feng Lin","doi":"10.1159/000534963","DOIUrl":"10.1159/000534963","url":null,"abstract":"Introduction: C3 is central for all complement activation pathways, thus making it an attractive therapeutic target. Many C3-targeted agents are under extensive development with one already approved for clinical use. However, most, if not all, C3 inhibitors are human or nonhuman primate C3-specific, making evaluating their efficacies in vivo before a clinical trial extremely difficult and costly.Methods: We first studied the compatibility of human C3 in the rat complement system, then developed a C3 humanized rat using the CRISPR/Cas9 technology. We thoroughly characterized the resultant human C3 humanized rats and tested the treatment efficacy of an established primate-specific C3 inhibitor in a model of complement-mediated hemolysis in the C3 humanized rats.Results: We found that supplementing human C3 protein into the C3-deficient rat blood restored its complement activity, which was inhibited by rat factor H or compstatin, suggesting that human C3 is compatible to the rat complement system. The newly developed C3 humanized rats appeared healthy and expressed human but not rat C3 without detectable spontaneous C3 activation. More importantly, complement-mediated hemolysis in the C3 humanized rats was also inhibited by compstatin both in vitro and in vivo.Conclusion: The successfully developed C3 humanized rats provided a much-desired rodent model to evaluate novel C3 inhibitors in vivo as potential drugs.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10786584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460291","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

Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection. 小鼠核糖核酸酶 6 限制了实验性尿路感染过程中的细菌扩散

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-05-14 DOI: 10.1159/000539177

Hanna Cortado, Macie Kercsmar, Birong Li, Gabriela Vasquez-Martinez, Sudipti Gupta, Christina Ching, Gregory Ballash, Israel Cotzomi-Ortega, Yuriko I Sanchez-Zamora, Ester Boix, Diana Zepeda-Orozco, Ashley R Jackson, John David Spencer, Juan de Dios Ruiz-Rosado, Brian Becknell

{"title":"Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection.","authors":"Hanna Cortado, Macie Kercsmar, Birong Li, Gabriela Vasquez-Martinez, Sudipti Gupta, Christina Ching, Gregory Ballash, Israel Cotzomi-Ortega, Yuriko I Sanchez-Zamora, Ester Boix, Diana Zepeda-Orozco, Ashley R Jackson, John David Spencer, Juan de Dios Ruiz-Rosado, Brian Becknell","doi":"10.1159/000539177","DOIUrl":"10.1159/000539177","url":null,"abstract":"Introduction: The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli (UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI.Methods: We generated a Rnase6EGFP knock-in allele to identify cellular sources of Rnase6 and determine the consequences of homozygous Rnase6 deletion on antimicrobial activity and UTI susceptibility.Results: We identified monocytes and macrophages as the primary cellular sources of Rnase6 in bladders and kidneys of Rnase6EGFP/+ mice. Rnase6 deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+ controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages.Conclusion: Our findings establish that RNase6 prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922428","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

Obituary of Prof. Uli Theopold, 1957-2023. 乌利-西奥波德教授的讣告，1957-2023。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI: 10.1159/000535642

Ylva Engström, Bruno Lemaitre, Dan Hultmark

引用次数: 0

Unraveling the Intricate Web: Complement Activation Shapes the Pathogenesis of Sepsis-Induced Coagulopathy. 揭开错综复杂的网络：补体激活决定败血症诱发凝血病的发病机制

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-05-31 DOI: 10.1159/000539502

Xin Wei, Ye Tu, Shuhong Bu, Guimei Guo, Hongbin Wang, Zhibin Wang

{"title":"Unraveling the Intricate Web: Complement Activation Shapes the Pathogenesis of Sepsis-Induced Coagulopathy.","authors":"Xin Wei, Ye Tu, Shuhong Bu, Guimei Guo, Hongbin Wang, Zhibin Wang","doi":"10.1159/000539502","DOIUrl":"10.1159/000539502","url":null,"abstract":"Background: Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in severe cases manifests as disseminated intravascular coagulation (DIC), or even develops into multiple organ dysfunction syndrome (MODS). The complement system and the coagulation system as the main columns of innate immunity and hemostasis, respectively, undergo substantial activation after sepsis.Summary: Dysfunction of the complement, coagulation/fibrinolytic cascades caused by sepsis leads to \"thromboinflammation,\" which ultimately amplifies the systemic inflammatory response and accelerates the development of MODS. Recent studies have revealed that massive activation of the complement system exacerbates sepsis-induced coagulation and even results in DIC, which suggests that inhibition of complement activation may have therapeutic potential in the treatment of septic coagulopathy.Key messages: Sepsis-associated thrombosis involves the upregulation or activation of procoagulant factors, down-regulation or inactivation of anticoagulant factors, and impairment of the fibrinolytic mechanism. This review aims to summarize the latest literature and analyze the underlying molecular mechanisms of the activation of the complement system on the abnormal coagulation cascades in sepsis.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179136","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

Immunometabolic Regulation of Bacterial Infection, Biofilms, and Antibiotic Susceptibility. 细菌感染、生物膜和抗生素敏感性的免疫代谢调节。

IF 5.3 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-02-03 DOI: 10.1159/000536649

Ying-Tsun Chen, Gaurav Kumar Lohia, Samantha Chen, Sebastián A Riquelme

{"title":"Immunometabolic Regulation of Bacterial Infection, Biofilms, and Antibiotic Susceptibility.","authors":"Ying-Tsun Chen, Gaurav Kumar Lohia, Samantha Chen, Sebastián A Riquelme","doi":"10.1159/000536649","DOIUrl":"10.1159/000536649","url":null,"abstract":"Background: Upon infection, mucosal tissues activate a brisk inflammatory response to clear the pathogen, i.e., resistance to disease. Resistance to disease is orchestrated by tissue-resident macrophages, which undergo profound metabolic reprogramming after sensing the pathogen. These metabolically activated macrophages release many inflammatory factors, which promote their bactericidal function. However, in immunocompetent individuals, pathogens like Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella evade this type of immunity, generating communities that thrive for the long term.Summary: These organisms develop features that render them less susceptible to eradication, such as biofilms and increased tolerance to antibiotics. Furthermore, after antibiotic therapy withdrawal, \"persister\" cells rapidly upsurge, triggering inflammatory relapses that worsen host health. How these pathogens persisted in inflamed tissues replete with activated macrophages remains poorly understood.Key messages: In this review, we discuss recent findings indicating that the ability of P. aeruginosa, S. aureus, and Salmonella to evolve biofilms and antibiotic tolerance is promoted by the similar metabolic routes that regulate macrophage metabolic reprogramming.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10914382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681200","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