Pub Date : 2024-01-01Epub Date: 2024-02-03DOI: 10.1159/000536649
Ying-Tsun Chen, Gaurav Kumar Lohia, Samantha Chen, Sebastián A Riquelme
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.
{"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":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p><p><strong>Key messages: </strong>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.</p>","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}
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.
引言由冠状病毒 2(SARS-CoV-2)引起的 2019 年冠状病毒病(COVID-19)已成为一种咄咄逼人的病毒性流行病。医疗保健提供者面临着一项具有挑战性的任务,即迅速制定有效的策略来应对这一疾病及其长期后果。病毒进入宿主细胞涉及穗状(S)蛋白 S1 亚基的受体结合域(RBD)与宿主细胞上的血管紧张素转换酶(ACE)之间的相互作用。甘油醛-3-磷酸脱氢酶(GAPDH)是一种参与细胞糖酵解能量代谢和微量营养素平衡的兼职酶。它存在于各种细胞区和细胞外环境中。尽管人们知道它是哺乳动物先天免疫防御机制的一个组成部分,但迄今为止,它在病毒限制中的作用仍然未知:方法:使用重组 S 蛋白、受体结合域(RBD)和人 GAPDH 蛋白进行固相结合测定和生物层干涉测量(BLI)。表达 S 蛋白四种不同株系变体的伪病毒颗粒均携带 ZsGreen 基因作为感染标记,用于基于流式细胞仪的感染性检测:结果:在细胞外培养基中加入人 GAPDH 能显著抑制伪病毒进入培养的靶细胞。结合试验表明,人 GAPDH 与 SARS-CoV-2 的 S 蛋白和 RBD 结构域结合的亲和力为纳米级:我们的研究表明,GAPDH 的这种相互作用会干扰病毒与 hACE2 受体的对接,从而影响病毒进入哺乳动物细胞。
{"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":"<p><strong>Introduction: </strong>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.</p><p><strong>Method: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Our investigations suggest that this interaction of GAPDH interferes in the viral docking with hACE2 receptors, thereby affecting viral ingress into mammalian cells.</p>","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/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}
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.
{"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":"<p><strong>Background: </strong>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.</p><p><strong>Summary: </strong>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.</p><p><strong>Key messages: </strong>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.</p>","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/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}
Pub Date : 2024-01-01Epub Date: 2024-01-08DOI: 10.1159/000535642
Ylva Engström, Bruno Lemaitre, Dan Hultmark
{"title":"Obituary of Prof. Uli Theopold, 1957-2023.","authors":"Ylva Engström, Bruno Lemaitre, Dan Hultmark","doi":"10.1159/000535642","DOIUrl":"10.1159/000535642","url":null,"abstract":"","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/PMC10773639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403186","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}
Pub Date : 2024-01-01Epub Date: 2024-01-17DOI: 10.1159/000535793
Sarah Truthe, Tilman E Klassert, Stefan Schmelz, Danny Jonigk, Wulf Blankenfeldt, Hortense Slevogt
Background: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role in the genesis of atherosclerosis. Recent research has shown its involvement in cancer, ischemic stroke, and diabetes. LOX-1 is a C-type lectin receptor and is involved in the activation of immune cells and inflammatory processes. It may further interact with pathogens, suggesting a role in infections or the host's response.
Summary: This review compiles the current knowledge of potential implications of LOX-1 in inflammatory processes and in host-pathogen interactions with a particular emphasis on its regulatory role in immune responses. Also discussed are genomic and structural variations found in LOX-1 homologs across different species as well as potential involvements of LOX-1 in inflammatory processes from the angle of different cell types and organ-specific interactions.
Key messages: The results presented reveal both similar and different structures in human and murine LOX-1 and provide clues as to the possible origins of different modes of interaction. These descriptions raise concerns about the suitability, particularly of mouse models, that are often used in the analysis of its functionality in humans. Further research should also aim to better understand the mostly unknown binding and interaction mechanisms between LOX-1 and different pathogens. This pursuit will not only enhance our understanding of LOX-1 involvement in inflammatory processes but also identify potential targets for immunomodulatory approaches.
{"title":"Role of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Inflammation and Pathogen-Associated Interactions.","authors":"Sarah Truthe, Tilman E Klassert, Stefan Schmelz, Danny Jonigk, Wulf Blankenfeldt, Hortense Slevogt","doi":"10.1159/000535793","DOIUrl":"10.1159/000535793","url":null,"abstract":"<p><strong>Background: </strong>Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is known as a major receptor for oxidized low-density lipoproteins (oxLDL) and plays a significant role in the genesis of atherosclerosis. Recent research has shown its involvement in cancer, ischemic stroke, and diabetes. LOX-1 is a C-type lectin receptor and is involved in the activation of immune cells and inflammatory processes. It may further interact with pathogens, suggesting a role in infections or the host's response.</p><p><strong>Summary: </strong>This review compiles the current knowledge of potential implications of LOX-1 in inflammatory processes and in host-pathogen interactions with a particular emphasis on its regulatory role in immune responses. Also discussed are genomic and structural variations found in LOX-1 homologs across different species as well as potential involvements of LOX-1 in inflammatory processes from the angle of different cell types and organ-specific interactions.</p><p><strong>Key messages: </strong>The results presented reveal both similar and different structures in human and murine LOX-1 and provide clues as to the possible origins of different modes of interaction. These descriptions raise concerns about the suitability, particularly of mouse models, that are often used in the analysis of its functionality in humans. Further research should also aim to better understand the mostly unknown binding and interaction mechanisms between LOX-1 and different pathogens. This pursuit will not only enhance our understanding of LOX-1 involvement in inflammatory processes but also identify potential targets for immunomodulatory approaches.</p>","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/PMC10866614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485735","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}
Pub Date : 2024-01-01Epub Date: 2024-02-26DOI: 10.1159/000536357
Cécile Guth, Pia Philippa Schumacher, Archena Vijayakumar, Hannah Borgmann, Helene Balles, Marianne Koschel, Frederic Risch, Benjamin Lenz, Achim Hoerauf, Marc P Hübner, Jesuthas Ajendra
Introduction: Interleukin-4 (IL-4) is a central regulator of type 2 immunity, crucial for the defense against multicellular parasites like helminths. This study focuses on its roles and cellular sources during Litomosoides sigmodontis infection, a model for human filarial infections.
Methods: Utilizing an IL-4 secretion assay, investigation into the sources of IL-4 during the progression of L. sigmodontis infection was conducted. The impact of eosinophils on the Th2 response was investigated through experiments involving dblGATA mice, which lack eosinophils and, consequently, eosinophil-derived IL-4.
Results: The absence of eosinophils notably influenced Th2 polarization, leading to impaired production of type 2 cytokines. Interestingly, despite this eosinophil deficiency, macrophage polarization, proliferation, and antibody production remained unaffected.
Conclusion: Our research uncovers eosinophils as a major source of IL-4, especially during the early phase of filarial infection. Consequently, these findings shed new light on IL-4 dynamics and eosinophil effector functions in filarial infections.
{"title":"Eosinophils Are an Endogenous Source of Interleukin-4 during Filarial Infections and Contribute to the Development of an Optimal T Helper 2 Response.","authors":"Cécile Guth, Pia Philippa Schumacher, Archena Vijayakumar, Hannah Borgmann, Helene Balles, Marianne Koschel, Frederic Risch, Benjamin Lenz, Achim Hoerauf, Marc P Hübner, Jesuthas Ajendra","doi":"10.1159/000536357","DOIUrl":"10.1159/000536357","url":null,"abstract":"<p><strong>Introduction: </strong>Interleukin-4 (IL-4) is a central regulator of type 2 immunity, crucial for the defense against multicellular parasites like helminths. This study focuses on its roles and cellular sources during Litomosoides sigmodontis infection, a model for human filarial infections.</p><p><strong>Methods: </strong>Utilizing an IL-4 secretion assay, investigation into the sources of IL-4 during the progression of L. sigmodontis infection was conducted. The impact of eosinophils on the Th2 response was investigated through experiments involving dblGATA mice, which lack eosinophils and, consequently, eosinophil-derived IL-4.</p><p><strong>Results: </strong>The absence of eosinophils notably influenced Th2 polarization, leading to impaired production of type 2 cytokines. Interestingly, despite this eosinophil deficiency, macrophage polarization, proliferation, and antibody production remained unaffected.</p><p><strong>Conclusion: </strong>Our research uncovers eosinophils as a major source of IL-4, especially during the early phase of filarial infection. Consequently, these findings shed new light on IL-4 dynamics and eosinophil effector functions in filarial infections.</p>","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/PMC10932553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735439","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}
Introduction: The role of vitamin in COVID-19 remains controversial. We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation.
Methods: 25(OH)D3 in serum was associated with disease severity and outcome in 190 COVID-19 patients. In a COVID-19 animal model using intravenous injection of plasma from patients with COVID-19 acute respiratory distress syndrome into C57/BL6 mice, mice were treated with 0.25 μg human 1,25(OH)D3 or vehicle. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Changes in gene expression after vitamin D supplementation were measured.
Results: Vitamin D deficiency and insufficiency were associated with increased severity and unfavorable outcome after 28 days. Vitamin D levels were negatively associated with biomarkers of COVID-19 severity. Vitamin D supplementation after challenge of mice with COVID-19 plasma led to reduced levels of TNFα, IL-6, IFNγ, and MPO in the lung, as well as down-regulation of pro-inflammatory pathways.
Conclusion: Normal levels of endogenous vitamin D are associated with reduced severity and risk of unfavorable outcome in COVID-19, possibly through attenuation of tissue-specific hyperinflammation.
{"title":"Association of Vitamin D with Severity and Outcome of COVID-19: Clinical and Experimental Evidence.","authors":"Georgios Renieris, Spyros Foutadakis, Theano Andriopoulou, Victoria-Marina Spanou, Dionyssia-Eirini Droggiti, Dionysios Kafousopoulos, Theologia Gkavogianni, Georgia Damoraki, Giannis Vatsellas, Evangelos J Giamarellos-Bourboulis","doi":"10.1159/000535302","DOIUrl":"10.1159/000535302","url":null,"abstract":"<p><strong>Introduction: </strong>The role of vitamin in COVID-19 remains controversial. We investigated the association between endogenous vitamin D and the severity of COVID-19 as well as the mechanisms of action of vitamin D supplementation.</p><p><strong>Methods: </strong>25(OH)D3 in serum was associated with disease severity and outcome in 190 COVID-19 patients. In a COVID-19 animal model using intravenous injection of plasma from patients with COVID-19 acute respiratory distress syndrome into C57/BL6 mice, mice were treated with 0.25 μg human 1,25(OH)D3 or vehicle. Mice were sacrificed on day 4. Cytokines and myeloperoxidase (MPO) in tissues were measured. Changes in gene expression after vitamin D supplementation were measured.</p><p><strong>Results: </strong>Vitamin D deficiency and insufficiency were associated with increased severity and unfavorable outcome after 28 days. Vitamin D levels were negatively associated with biomarkers of COVID-19 severity. Vitamin D supplementation after challenge of mice with COVID-19 plasma led to reduced levels of TNFα, IL-6, IFNγ, and MPO in the lung, as well as down-regulation of pro-inflammatory pathways.</p><p><strong>Conclusion: </strong>Normal levels of endogenous vitamin D are associated with reduced severity and risk of unfavorable outcome in COVID-19, possibly through attenuation of tissue-specific hyperinflammation.</p>","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/PMC10764091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440779","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}
Introduction: Toll-like receptors play crucial roles in the sepsis-induced systemic inflammatory response. Septic shock mortality correlates with overexpression of neutrophilic TLR2 and TLR9, while the role of TLR4 overexpression remains a debate. In addition, TLRs are involved in the pathogenesis of viral infections such as COVID-19, where the single-stranded RNA of SARS-CoV-2 is recognized by TLR7 and TLR8, and the spike protein activates TLR4.
Methods: In this study, we conducted a comprehensive analysis of TLRs 1-10 expressions in white blood cells from 71 patients with bacterial and viral infections. Patients were divided into 4 groups based on disease type and severity (sepsis, septic shock, moderate, and severe COVID-19) and compared to 7 healthy volunteers.
Results: We observed a significant reduction in the expression of TLR4 and its co-receptor CD14 in septic shock neutrophils compared to the control group (p < 0.001). Severe COVID-19 patients exhibited a significant increase in TLR3 and TLR7 levels in neutrophils compared to controls (p < 0.05). Septic shock patients also showed a similar increase in TLR7 in neutrophils along with elevated intermediate monocytes (CD14+CD16+) compared to the control group (p < 0.005 and p < 0.001, respectively). However, TLR expression remained unchanged in lymphocytes.
Conclusion: This study provides further insights into the mechanisms of TLR activation in various infectious conditions. Additional analysis is needed to assess their correlation with patient outcome and to evaluate the impact of TLR-pathway modulation during septic shock and severe COVID-19.
{"title":"TLRs1-10 Protein Expression in Circulating Human White Blood Cells during Bacterial and COVID-19 Infections.","authors":"Louise Chomel, Mathieu Vogt, Julien Demiselle, Pierrick Le Borgne, Marine Tschirhart, Valentin Morandeau, Hamid Merdji, Laurent Miguet, Julie Helms, Ferhat Meziani, Laurent Mauvieux","doi":"10.1159/000536593","DOIUrl":"10.1159/000536593","url":null,"abstract":"<p><strong>Introduction: </strong>Toll-like receptors play crucial roles in the sepsis-induced systemic inflammatory response. Septic shock mortality correlates with overexpression of neutrophilic TLR2 and TLR9, while the role of TLR4 overexpression remains a debate. In addition, TLRs are involved in the pathogenesis of viral infections such as COVID-19, where the single-stranded RNA of SARS-CoV-2 is recognized by TLR7 and TLR8, and the spike protein activates TLR4.</p><p><strong>Methods: </strong>In this study, we conducted a comprehensive analysis of TLRs 1-10 expressions in white blood cells from 71 patients with bacterial and viral infections. Patients were divided into 4 groups based on disease type and severity (sepsis, septic shock, moderate, and severe COVID-19) and compared to 7 healthy volunteers.</p><p><strong>Results: </strong>We observed a significant reduction in the expression of TLR4 and its co-receptor CD14 in septic shock neutrophils compared to the control group (p < 0.001). Severe COVID-19 patients exhibited a significant increase in TLR3 and TLR7 levels in neutrophils compared to controls (p < 0.05). Septic shock patients also showed a similar increase in TLR7 in neutrophils along with elevated intermediate monocytes (CD14+CD16+) compared to the control group (p < 0.005 and p < 0.001, respectively). However, TLR expression remained unchanged in lymphocytes.</p><p><strong>Conclusion: </strong>This study provides further insights into the mechanisms of TLR activation in various infectious conditions. Additional analysis is needed to assess their correlation with patient outcome and to evaluate the impact of TLR-pathway modulation during septic shock and severe COVID-19.</p>","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/PMC11001289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094203","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}
Hang Zhao, Wenhua Li, Xin Zhou, Liang Pan, Yun Feng, Pingyu Gao, Jie Ji, Huanyan Zhang, Kai Zhao, Chi Wang, Zhanjun Lu
Introduction: C-X-C motif chemokine ligand 1 (CXCL1) is a potent neutrophil chemoattractant that plays a pivotal role in recruiting neutrophils during inflammatory conditions. This study explored the role of CXCL1 in modulating the gut microbiota, influencing neutrophil infiltration, and contributing to the development of colitis. Methods: We employed quantitative PCR to assess CXCL1 expression in colon samples. A mouse model of DSS-induced colitis was utilized to explore the progression of colitis in wild-type (WT) and CXCL1-deficient (CXCL1-/-) mice. Results: Colitis attenuation was evident in CXCL1-/- mice. Significant alterations were observed in the gut microbiome, as revealed by 16S rRNA gene sequencing. Furthermore, CXCL1-/- mice exhibited reduced gut permeability and diminished endotoxin levels in peripheral blood following DSS treatment compared to WT mice. In response to DSS treatment, WT mice showed a clear increase in neutrophil infiltration, while CXCL1-/- mice exhibited lower levels of infiltration. FMT using stools from CXCL1-/- mice alleviated DSS-induced colitis. Interestingly, FMT from patients with colitis increased CXCL1 and Ly6G expression in colons of gut-sterilized mice. Clinical data analysis revealed elevated CXCL1 and CD15 expression in patients with colitis, with a positive correlation between the severity of colitis and the expression of CXCL1 and CD15. Conclusion: These findings shed light on the pivotal role of CXCL1 in promoting colitis by modulating the gut microbiota.
{"title":"C-X-C motif chemokine ligand 1 promotes colitis by modulating the gut microbiota","authors":"Hang Zhao, Wenhua Li, Xin Zhou, Liang Pan, Yun Feng, Pingyu Gao, Jie Ji, Huanyan Zhang, Kai Zhao, Chi Wang, Zhanjun Lu","doi":"10.1159/000535637","DOIUrl":"https://doi.org/10.1159/000535637","url":null,"abstract":"Introduction: C-X-C motif chemokine ligand 1 (CXCL1) is a potent neutrophil chemoattractant that plays a pivotal role in recruiting neutrophils during inflammatory conditions. This study explored the role of CXCL1 in modulating the gut microbiota, influencing neutrophil infiltration, and contributing to the development of colitis. \u0000Methods: We employed quantitative PCR to assess CXCL1 expression in colon samples. A mouse model of DSS-induced colitis was utilized to explore the progression of colitis in wild-type (WT) and CXCL1-deficient (CXCL1-/-) mice. \u0000Results: Colitis attenuation was evident in CXCL1-/- mice. Significant alterations were observed in the gut microbiome, as revealed by 16S rRNA gene sequencing. Furthermore, CXCL1-/- mice exhibited reduced gut permeability and diminished endotoxin levels in peripheral blood following DSS treatment compared to WT mice. In response to DSS treatment, WT mice showed a clear increase in neutrophil infiltration, while CXCL1-/- mice exhibited lower levels of infiltration. FMT using stools from CXCL1-/- mice alleviated DSS-induced colitis. Interestingly, FMT from patients with colitis increased CXCL1 and Ly6G expression in colons of gut-sterilized mice. Clinical data analysis revealed elevated CXCL1 and CD15 expression in patients with colitis, with a positive correlation between the severity of colitis and the expression of CXCL1 and CD15. \u0000Conclusion: These findings shed light on the pivotal role of CXCL1 in promoting colitis by modulating the gut microbiota.\u0000","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138587955","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}
Geburtshilfe und Frauenheilkunde 48 (1988) , (Heft 6/88) P. Wieacker, P. Peters, M. Breckwoldt: Gonnadotropinresistenz beim Rothmund-Thomson-Syndrom
{"title":"Erratum.","authors":"","doi":"10.1159/000530893","DOIUrl":"https://doi.org/10.1159/000530893","url":null,"abstract":"Geburtshilfe und Frauenheilkunde 48 (1988) , (Heft 6/88) P. Wieacker, P. Peters, M. Breckwoldt: Gonnadotropinresistenz beim Rothmund-Thomson-Syndrom","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663774","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}