Journal of Innate Immunity最新文献_第4页

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":" ","pages":"283-294"},"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

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":" ","pages":"295-323"},"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

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

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":" ","pages":"56-65"},"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

Innate Immune Response to Monkeypox Virus Infection: Mechanisms and Immune Escape. 对 MPOX 感染的先天免疫反应：机制与免疫逃逸

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-08-13 DOI: 10.1159/000540815

Reza Parnian, Fatemeh Heydarifard, Fatemeh Sadat Mousavi, Zahra Heydarifard, Milad Zandi

{"title":"Innate Immune Response to Monkeypox Virus Infection: Mechanisms and Immune Escape.","authors":"Reza Parnian, Fatemeh Heydarifard, Fatemeh Sadat Mousavi, Zahra Heydarifard, Milad Zandi","doi":"10.1159/000540815","DOIUrl":"10.1159/000540815","url":null,"abstract":"Background: The reemergence of monkeypox virus (Mpox, formerly monkeypox) in 2022 in non-endemic countries has raised significant concerns for global health due to its high transmissibility and mortality rate. A major challenge in combating Mpox is its ability to evade the host's innate immune system, the first line of defense against viral infections.Summary: Mpox encodes various proteins that interfere with key antiviral pathways and mechanisms, such as the nuclear factor kappa B signaling, cytokine production, complement and inflammasome activation, and chemokine binding. These proteins modulate the expression and function of innate immune mediators, such as interferons, interleukins, and Toll-like receptors, and impair the recruitment and activation of innate immune cells, such as natural killer cells. By suppressing or altering these innate immune responses, Mpox enhances its replication and infection in the host tissues and organs, leading to systemic inflammation, tissue damage, and organ failure.Key messages: This study reveals new insights into the molecular and cellular interactions between Mpox and the host's innate immune system. It identifies potential targets and strategies for antiviral interventions, highlighting the importance of understanding these interactions to develop effective treatments and improve global health responses to Mpox outbreaks.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"413-424"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975860","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":" ","pages":"143-158"},"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

Glyceraldehyde-3-Phosphate Dehydrogenase Binds with Spike Protein and Inhibits the Entry of SARS-CoV-2 into Host Cells. 甘油醛-3-磷酸脱氢酶（GAPDH）与尖峰蛋白结合，抑制 SARS-CoV-2 进入宿主细胞。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-02-07 DOI: 10.1159/000535634

Rahul Dilawari, Gaurav Kumar Chaubey, Radheshyam Modanwal, Asmita Dhiman, Sharmila Talukdar, Ajay Kumar, Chaaya Iyengar Raje, Manoj Raje

{"title":"Glyceraldehyde-3-Phosphate Dehydrogenase Binds with Spike Protein and Inhibits the Entry of SARS-CoV-2 into Host Cells.","authors":"Rahul Dilawari, Gaurav Kumar Chaubey, Radheshyam Modanwal, Asmita Dhiman, Sharmila Talukdar, Ajay Kumar, Chaaya Iyengar Raje, Manoj Raje","doi":"10.1159/000535634","DOIUrl":"10.1159/000535634","url":null,"abstract":"Introduction: Coronavirus disease 2019 caused by coronavirus-2 (SARS-CoV-2) has emerged as an aggressive viral pandemic. Health care providers confront a challenging task for rapid development of effective strategies to combat this and its long-term after effects. Virus entry into host cells involves interaction between receptor-binding domain (RBD) of spike (S) protein S1 subunit with angiotensin converting enzyme present on host cells. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a moonlighting enzyme involved in cellular glycolytic energy metabolism and micronutrient homeostasis. It is deployed in various cellular compartments and the extra cellular milieu. Though it is known to moonlight as a component of mammalian innate immune defense machinery, till date its role in viral restriction remains unknown.Method: Recombinant S protein, the RBD, and human GAPDH protein were used for solid phase binding assays and biolayer interferometry. Pseudovirus particles expressing four different strain variants of S protein all harboring ZsGreen gene as marker of infection were used for flow cytometry-based infectivity assays.Results: Pseudovirus entry into target cells in culture was significantly inhibited by addition of human GAPDH into the extracellular medium. Binding assays demonstrated that human GAPDH binds to S protein and RBD of SARS-CoV-2 with nanomolar affinity.Conclusions: Our investigations suggest that this interaction of GAPDH interferes in the viral docking with hACE2 receptors, thereby affecting viral ingress into mammalian cells.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"133-142"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10911789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702696","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

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":" ","pages":"337-353"},"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

TLR2 and NLRP3 Orchestrate Regulatory Roles in Escherichia coli Infection-Induced Septicemia in Mouse Models. TLR2 和 NLRP3 在大肠埃希菌感染诱发的小鼠模型败血症中发挥调节作用。

IF 4.7 3区医学

Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-10-15 DOI: 10.1159/000541819

Zhiguo Gong, Wei Mao, Jiamin Zhao, Peipei Ren, Zhuoya Yu, Yunjie Bai, Chao Wang, Yuze Liu, Shuang Feng, Surong Hasi

{"title":"TLR2 and NLRP3 Orchestrate Regulatory Roles in Escherichia coli Infection-Induced Septicemia in Mouse Models.","authors":"Zhiguo Gong, Wei Mao, Jiamin Zhao, Peipei Ren, Zhuoya Yu, Yunjie Bai, Chao Wang, Yuze Liu, Shuang Feng, Surong Hasi","doi":"10.1159/000541819","DOIUrl":"10.1159/000541819","url":null,"abstract":"Introduction: Escherichia coli (E. coli) is a significant commensal gram-negative bacterium that can give rise to various diseases. The roles of Toll-like receptor 2 (TLR2) and the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in sepsis induced by E. coli infection remain unclear.Methods: In vivo, we investigated differences in mortality, production of inflammatory mediators, organ damage, neutrophil count, and bacterial load during E. coli infection in C57BL/6J mice, as well as in mice deficient in TLR2 or NLRP3. In vitro, we investigated the impact of E. coli on the activation of TLR2 and NLRP3 in macrophages and the influence of TLR2 and NLRP3 on the activation of inflammatory signaling pathways and the secretion of inflammatory mediators in macrophages induced by E. coli infection.Results: TLR2-deficient (TLR2-/-) and NLRP3-deficient (NLRP3-/-) mice exhibit significantly increased mortality and organ damage after E. coli infection. These mice also show elevated levels of TNF-α and IL-10 in serum and peritoneal lavage fluid. Additionally, TLR2-/- and NLRP3-/- mice display heightened neutrophil recruitment and increased bacterial load in the blood. Furthermore, macrophages from these mice demonstrate a significant reduction in the activation of the MAPK signaling pathway.Conclusion: TLR2 and NLRP3 play crucial roles in modulating inflammatory mediator expression, immune cell recruitment, and bactericidal activity, thereby preventing excessive tissue damage and reducing mortality in E. coli-induced sepsis.","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":" ","pages":"513-528"},"PeriodicalIF":4.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467606","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 5.3 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