B cells can have a wide range of pro- and anti- inflammatory functions. A subset of B cells called regulatory B cells (Bregs) can potently suppress immune responses. Bregs have been shown to maintain immune homeostasis and modulate inflammatory responses. Bregs are an exciting cellular target across a range of diseases, including Breg induction in autoimmunity, allergy and transplantation, and Breg suppression in cancers and infection. Bregs exhibit a remarkable phenotypic heterogeneity, rendering their unequivocal identification a challenging task. The lack of a universally accepted and exclusive surface marker set for Bregs across various studies contributes to inconsistencies in their categorization. This review paper presents a comprehensive overview of the current understanding of the phenotypic and functional properties of human Bregs while addressing the persisting ambiguities and discrepancies in their characterization. Finally, the paper examines the promising therapeutic opportunities presented by Bregs as their immunomodulatory capacities have gained attention in the context of autoimmune diseases, allergic conditions, and cancer. We explore the exciting potential in harnessing Bregs as potential therapeutic agents and the avenues that remain open for the development of Breg-based treatment strategies.
B 细胞具有多种促炎和抗炎功能。被称为调节性 B 细胞(Bregs)的 B 细胞亚群可有效抑制免疫反应。研究表明,Bregs 可维持免疫平衡并调节炎症反应。Bregs 是一系列疾病中令人兴奋的细胞靶点,包括自身免疫、过敏和移植中的 Breg 诱导,以及癌症和感染中的 Breg 抑制。Bregs 具有显著的表型异质性,因此明确识别它们是一项具有挑战性的任务。在各种研究中,Bregs 缺乏普遍接受的专属表面标记集,这也是导致其分类不一致的原因之一。本综述论文全面概述了目前对人类 Bregs 表型和功能特性的理解,同时探讨了其特征描述中持续存在的模糊性和差异。最后,本文探讨了 Bregs 带来的治疗机会,因为它们在自身免疫性疾病、过敏性疾病和癌症方面的免疫调节能力已引起人们的关注。我们探讨了利用 Bregs 作为潜在治疗药物的令人兴奋的潜力,以及开发基于 Breg 的治疗策略的途径。
{"title":"The current understanding of the phenotypic and functional properties of human regulatory B cells (Bregs).","authors":"Nawara Faiza Ahsan, Stella Lourenço, Dimitra Psyllou, Alexander Long, Sushma Shankar, Rachael Bashford-Rogers","doi":"10.1093/oxfimm/iqae012","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae012","url":null,"abstract":"<p><p>B cells can have a wide range of pro- and anti- inflammatory functions. A subset of B cells called regulatory B cells (Bregs) can potently suppress immune responses. Bregs have been shown to maintain immune homeostasis and modulate inflammatory responses. Bregs are an exciting cellular target across a range of diseases, including Breg induction in autoimmunity, allergy and transplantation, and Breg suppression in cancers and infection. Bregs exhibit a remarkable phenotypic heterogeneity, rendering their unequivocal identification a challenging task. The lack of a universally accepted and exclusive surface marker set for Bregs across various studies contributes to inconsistencies in their categorization. This review paper presents a comprehensive overview of the current understanding of the phenotypic and functional properties of human Bregs while addressing the persisting ambiguities and discrepancies in their characterization. Finally, the paper examines the promising therapeutic opportunities presented by Bregs as their immunomodulatory capacities have gained attention in the context of autoimmune diseases, allergic conditions, and cancer. We explore the exciting potential in harnessing Bregs as potential therapeutic agents and the avenues that remain open for the development of Breg-based treatment strategies.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"5 1","pages":"iqae012"},"PeriodicalIF":0.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06eCollection Date: 2024-01-01DOI: 10.1093/oxfimm/iqae011
Yasmim Barcellos Madeira Rosa, Henrique Tamanini Silva Moschen, Ana Carolina Loss, Theresa Cristina Cardoso da Silva, Ana Paula Brioschi Dos Santos, Bruna Caetano Pimenta, Julia Sthefany Nunes Zordan, Crispim Cerutti Junior, Angelica Espinosa Barbosa Miranda, Iuri Drumond Louro, Débora Dummer Meira, Creuza Rachel Vicente
Espírito Santo state, in Brazil, is a dengue-endemic region predicted to suffer from an increase in temperature and drought due to climate change, which could affect the areas with active dengue virus transmission. The study objective was modeling climatic factors and climate change effects in zones suitable for dengue virus transmission in Espírito Santo state, Brazil. Data on dengue reports from 2022 were used to determine climatic variables related to spatial distribution. The climate change projections were generated for the 2030s, 2050s, 2070s, and 2090s for three distinct Shared Socioeconomic Pathways: SSP1-2.6, SSP2-4.5 and SSP5-8.5. A maximum entropy algorithm was used to construct the three models and projections, and the results were used to calculate the ensemble mean. Isothermality, the maximum temperature of the warmest month, precipitation of the wettest month, precipitation of the warmest quarter, and annual precipitation impacted the model. Projections indicated a change in areas suitable for dengue virus transmission, varying from -30.44% in the 2070s (SSP1-2.6) to +13.07% in the 2070s (SSP5-8.5) compared to 2022. The coastal regions were consistently suitable in all scenarios. Urbanized and highly populated areas were predicted to persist with active dengue transmission in Espírito Santo state, posing challenges for public health response.
{"title":"Climate change impacts on dengue transmission areas in Espírito Santo state, Brazil.","authors":"Yasmim Barcellos Madeira Rosa, Henrique Tamanini Silva Moschen, Ana Carolina Loss, Theresa Cristina Cardoso da Silva, Ana Paula Brioschi Dos Santos, Bruna Caetano Pimenta, Julia Sthefany Nunes Zordan, Crispim Cerutti Junior, Angelica Espinosa Barbosa Miranda, Iuri Drumond Louro, Débora Dummer Meira, Creuza Rachel Vicente","doi":"10.1093/oxfimm/iqae011","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae011","url":null,"abstract":"<p><p>Espírito Santo state, in Brazil, is a dengue-endemic region predicted to suffer from an increase in temperature and drought due to climate change, which could affect the areas with active dengue virus transmission. The study objective was modeling climatic factors and climate change effects in zones suitable for dengue virus transmission in Espírito Santo state, Brazil. Data on dengue reports from 2022 were used to determine climatic variables related to spatial distribution. The climate change projections were generated for the 2030s, 2050s, 2070s, and 2090s for three distinct Shared Socioeconomic Pathways: SSP1-2.6, SSP2-4.5 and SSP5-8.5. A maximum entropy algorithm was used to construct the three models and projections, and the results were used to calculate the ensemble mean. Isothermality, the maximum temperature of the warmest month, precipitation of the wettest month, precipitation of the warmest quarter, and annual precipitation impacted the model. Projections indicated a change in areas suitable for dengue virus transmission, varying from -30.44% in the 2070s (SSP1-2.6) to +13.07% in the 2070s (SSP5-8.5) compared to 2022. The coastal regions were consistently suitable in all scenarios. Urbanized and highly populated areas were predicted to persist with active dengue transmission in Espírito Santo state, posing challenges for public health response.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"5 1","pages":"iqae011"},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11398874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22eCollection Date: 2024-01-01DOI: 10.1093/oxfimm/iqae009
Orestis Katsoulis, Oliver R Pitts, Aran Singanayagam
The existence of commensal fungi that reside within the respiratory tract, termed the airway mycobiome, has only recently been discovered. Studies are beginning to characterize the spectrum of fungi that inhabit the human upper and lower respiratory tract but heterogeneous sampling and analysis techniques have limited the generalizability of findings to date. In this review, we discuss existing studies that have examined the respiratory mycobiota in healthy individuals and in those with inflammatory lung conditions such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. Associations between specific fungi and features of disease pathogenesis are emerging but the precise functional consequences imparted by mycobiota upon the immune system remain poorly understood. It is imperative that further research is conducted in this important area as a more detailed understanding could facilitate the development of novel approaches to manipulating the mycobiome for therapeutic benefit.
{"title":"The airway mycobiome and interactions with immunity in health and chronic lung disease.","authors":"Orestis Katsoulis, Oliver R Pitts, Aran Singanayagam","doi":"10.1093/oxfimm/iqae009","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae009","url":null,"abstract":"<p><p>The existence of commensal fungi that reside within the respiratory tract, termed the airway mycobiome, has only recently been discovered. Studies are beginning to characterize the spectrum of fungi that inhabit the human upper and lower respiratory tract but heterogeneous sampling and analysis techniques have limited the generalizability of findings to date. In this review, we discuss existing studies that have examined the respiratory mycobiota in healthy individuals and in those with inflammatory lung conditions such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. Associations between specific fungi and features of disease pathogenesis are emerging but the precise functional consequences imparted by mycobiota upon the immune system remain poorly understood. It is imperative that further research is conducted in this important area as a more detailed understanding could facilitate the development of novel approaches to manipulating the mycobiome for therapeutic benefit.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"5 1","pages":"iqae009"},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-17eCollection Date: 2024-01-01DOI: 10.1093/oxfimm/iqae010
Kar On Cheng, Dolly E Montaño, Teresa Zelante, Axel Dietschmann, Mark S Gresnigt
Protective immunity to opportunistic fungal infections consists of tightly regulated innate and adaptive immune responses that clear the infection. Immune responses to infections of the vaginal mucosa by Candida species are, however, an exception. In the case of vulvovaginal candidiasis (VVC), the inflammatory response is associated with symptomatic disease, rather than that it results in pathogen clearance. As such VVC can be considered an inflammatory disease, which is a significant public health problem due to its predominance as a female-specific fungal infection. Particularly, women with recurrent VVC (RVVC) suffer from a significant negative impact on their quality of life and mental health. Knowledge of the inflammatory pathogenesis of (R)VVC may guide more effective diagnostic and therapeutic options to improve the quality of life of women with (R)VVC. Here, we review the immunopathogenesis of (R)VVC describing several elements that induce an inflammatory arson, starting with the activation threshold established by vaginal epithelial cells that prevent unnecessary ignition of inflammatory responses, epithelial and inflammasome-dependent immune responses. These inflammatory responses will drive neutrophil recruitment and dysfunctional neutrophil-mediated inflammation. We also review the, sometimes controversial, findings on the involvement of adaptive and systemic responses. Finally, we provide future perspectives on the potential of some unexplored cytokine axes and discuss whether VVC needs to be subdivided into subgroups to improve diagnosis and treatment.
{"title":"Inflammatory cytokine signalling in vulvovaginal candidiasis: a hot mess driving immunopathology.","authors":"Kar On Cheng, Dolly E Montaño, Teresa Zelante, Axel Dietschmann, Mark S Gresnigt","doi":"10.1093/oxfimm/iqae010","DOIUrl":"10.1093/oxfimm/iqae010","url":null,"abstract":"<p><p>Protective immunity to opportunistic fungal infections consists of tightly regulated innate and adaptive immune responses that clear the infection. Immune responses to infections of the vaginal mucosa by <i>Candida</i> species are, however, an exception. In the case of vulvovaginal candidiasis (VVC), the inflammatory response is associated with symptomatic disease, rather than that it results in pathogen clearance. As such VVC can be considered an inflammatory disease, which is a significant public health problem due to its predominance as a female-specific fungal infection. Particularly, women with recurrent VVC (RVVC) suffer from a significant negative impact on their quality of life and mental health. Knowledge of the inflammatory pathogenesis of (R)VVC may guide more effective diagnostic and therapeutic options to improve the quality of life of women with (R)VVC. Here, we review the immunopathogenesis of (R)VVC describing several elements that induce an inflammatory arson, starting with the activation threshold established by vaginal epithelial cells that prevent unnecessary ignition of inflammatory responses, epithelial and inflammasome-dependent immune responses. These inflammatory responses will drive neutrophil recruitment and dysfunctional neutrophil-mediated inflammation. We also review the, sometimes controversial, findings on the involvement of adaptive and systemic responses. Finally, we provide future perspectives on the potential of some unexplored cytokine axes and discuss whether VVC needs to be subdivided into subgroups to improve diagnosis and treatment.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"5 1","pages":"iqae010"},"PeriodicalIF":0.0,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142135096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-26eCollection Date: 2024-01-01DOI: 10.1093/oxfimm/iqae007
[This corrects the article DOI: 10.1093/oxfimm/iqae003.].
[此处更正了文章 DOI:10.1093/oxfimm/iqae003]。
{"title":"Correction to: <i>In-vitro</i> assessment of cutaneous immune responses to <i>aedes</i> mosquito salivary gland extract and dengue virus in Cambodian individuals.","authors":"","doi":"10.1093/oxfimm/iqae007","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae007","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/oxfimm/iqae003.].</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"5 1","pages":"iqae007"},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11281826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The gastrointestinal tract contains a diverse microbiome consisting of bacteria, fungi, viruses and archaea. Although these microbes usually reside as commensal organisms, it is now well established that higher abundance of specific bacterial or fungal species, or loss of diversity in the microbiome can significantly affect development, progression and outcomes in disease. Studies have mainly focused on the effects of bacteria, however, the impact of other microbes, such as fungi, has received increased attention in the last few years. Fungi only represent around 0.1% of the total gut microbial population. However, key fungal taxa such as Candida, Aspergillus and Wallemia have been shown to significantly impact health and disease. The composition of the gut mycobiome has been shown to affect immunity at distal sites, such as the heart, lung, brain, pancreas, and liver. In the case of the lung this phenomenon is referred to as the “gut-lung axis”. Recent studies have begun to explore and unveil the relationship between gut fungi and lung immunity in diseases such as asthma and lung cancer, and lung infections caused by viruses, bacteria and fungi. In this review we will summarise the current, rapidly growing, literature describing the impact of the gut mycobiome on respiratory disease and infection.
{"title":"The gut-lung axis: the impact of the gut mycobiome on pulmonary diseases and infections","authors":"Emily Sey, A. Warris","doi":"10.1093/oxfimm/iqae008","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae008","url":null,"abstract":"\u0000 The gastrointestinal tract contains a diverse microbiome consisting of bacteria, fungi, viruses and archaea. Although these microbes usually reside as commensal organisms, it is now well established that higher abundance of specific bacterial or fungal species, or loss of diversity in the microbiome can significantly affect development, progression and outcomes in disease. Studies have mainly focused on the effects of bacteria, however, the impact of other microbes, such as fungi, has received increased attention in the last few years. Fungi only represent around 0.1% of the total gut microbial population. However, key fungal taxa such as Candida, Aspergillus and Wallemia have been shown to significantly impact health and disease. The composition of the gut mycobiome has been shown to affect immunity at distal sites, such as the heart, lung, brain, pancreas, and liver. In the case of the lung this phenomenon is referred to as the “gut-lung axis”. Recent studies have begun to explore and unveil the relationship between gut fungi and lung immunity in diseases such as asthma and lung cancer, and lung infections caused by viruses, bacteria and fungi. In this review we will summarise the current, rapidly growing, literature describing the impact of the gut mycobiome on respiratory disease and infection.","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"12 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141808594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-14eCollection Date: 2024-01-01DOI: 10.1093/oxfimm/iqae006
Norifumi Iijima
The magnitude of the effector functions of memory T cells determines the consequences of the protection against invading pathogens and tumor development or the pathogenesis of autoimmune and allergic diseases. Tissue-resident memory T cells (TRM cells) are unique T-cell populations that persist in tissues for long periods awaiting re-encounter with their cognate antigen. Although TRM cell reactivation primarily requires the presentation of cognate antigens, recent evidence has shown that, in addition to the conventional concept, TRM cells can be reactivated without the presentation of cognate antigens. Non-cognate TRM cell activation is triggered by cross-reactive antigens or by several combinations of cytokines, including interleukin (IL)-2, IL-7, IL-12, IL-15 and IL-18. The activation mode of TRM cells reinforces their cytotoxic activity and promotes the secretion of effector cytokines (such as interferon-gamma and tumor necrosis factor-alpha). This review highlights the key features of TRM cell maintenance and reactivation and discusses the importance of effector functions that TRM cells exert upon being presented with cognate and/or non-cognate antigens, as well as cytokines secreted by TRM and non-TRM cells within the tissue microenvironment.
记忆 T 细胞效应功能的强弱决定了其对病原体入侵、肿瘤发生或自身免疫和过敏性疾病发病机制的保护作用。组织驻留记忆 T 细胞(TRM 细胞)是一种独特的 T 细胞群,可长期驻留在组织中,等待再次遇到它们的同源抗原。尽管TRM细胞的重新激活主要需要同源抗原的呈现,但最近的证据表明,除了传统概念外,TRM细胞还可以在没有同源抗原呈现的情况下被重新激活。交叉反应抗原或多种细胞因子组合(包括白细胞介素(IL)-2、IL-7、IL-12、IL-15 和 IL-18)可触发非同源TRM细胞活化。TRM细胞的活化模式可加强其细胞毒性活性,并促进效应细胞因子(如γ干扰素和肿瘤坏死因子-α)的分泌。本综述强调了TRM细胞维持和再激活的关键特征,并讨论了TRM细胞在出现同源和/或非同源抗原时发挥效应功能的重要性,以及TRM细胞和非TRM细胞在组织微环境中分泌的细胞因子。
{"title":"The emerging role of effector functions exerted by tissue-resident memory T cells.","authors":"Norifumi Iijima","doi":"10.1093/oxfimm/iqae006","DOIUrl":"10.1093/oxfimm/iqae006","url":null,"abstract":"<p><p>The magnitude of the effector functions of memory T cells determines the consequences of the protection against invading pathogens and tumor development or the pathogenesis of autoimmune and allergic diseases. Tissue-resident memory T cells (T<sub>RM</sub> cells) are unique T-cell populations that persist in tissues for long periods awaiting re-encounter with their cognate antigen. Although T<sub>RM</sub> cell reactivation primarily requires the presentation of cognate antigens, recent evidence has shown that, in addition to the conventional concept, T<sub>RM</sub> cells can be reactivated without the presentation of cognate antigens. Non-cognate T<sub>RM</sub> cell activation is triggered by cross-reactive antigens or by several combinations of cytokines, including interleukin (IL)-2, IL-7, IL-12, IL-15 and IL-18. The activation mode of T<sub>RM</sub> cells reinforces their cytotoxic activity and promotes the secretion of effector cytokines (such as interferon-gamma and tumor necrosis factor-alpha). This review highlights the key features of T<sub>RM</sub> cell maintenance and reactivation and discusses the importance of effector functions that T<sub>RM</sub> cells exert upon being presented with cognate and/or non-cognate antigens, as well as cytokines secreted by T<sub>RM</sub> and non-T<sub>RM</sub> cells within the tissue microenvironment.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"5 1","pages":"iqae006"},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11213632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vasile Mihai Sularea, Ruchi Sharma, David C Hay, Cliona O’Farrelly
Hepatotropic viruses are amongst the most ubiquitous pathogens worldwide, causing significant morbidity and mortality. As hepatocytes are among the primary targets of these viruses, their ability to mount early effective innate defence responses is of major research interest. Interferon lambda (IFNL) is produced early in response to viral stimulation in other cell types, but hepatocyte production of this interferon is little investigated. Due to the difficulty and significant costs in obtaining and culturing human primary hepatocytes, surrogate systems are widely sought. Here we used induced pluripotent stem (iPS)-derived hepatocyte-like cells (HLCs) to investigate hepatic IFNL expression in response to viral-like ligands. We demonstrate that hepatocytes rely on cytoplasmic pattern recognition receptors (PRRs) such as Protein Kinase RNA-dependent (PKR) and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLR) for the detection of double stranded RNA. Stimulation of HLCs by viral-like RNA ligands activating cytosolic RNA sensors resulted in thousand fold increase of type III interferon gene expression. These results are in contrast with type I IFN expression, which was induced to a lower extent. Concomitant induction of interferon stimulated genes, such as interferon-stimulated gene 15 (ISG15) and CXCL10, indicated the ability of HLCs to activate interferon-dependent activity. These results demonstrate that HLCs mount an innate antiviral response upon stimulation with viral-like RNA characterised by the induction of type III IFN.
{"title":"Early interferon lambda production is induced by double-stranded RNA in iPS-derived hepatocyte-like cells","authors":"Vasile Mihai Sularea, Ruchi Sharma, David C Hay, Cliona O’Farrelly","doi":"10.1093/oxfimm/iqae004","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae004","url":null,"abstract":"\u0000 Hepatotropic viruses are amongst the most ubiquitous pathogens worldwide, causing significant morbidity and mortality. As hepatocytes are among the primary targets of these viruses, their ability to mount early effective innate defence responses is of major research interest. Interferon lambda (IFNL) is produced early in response to viral stimulation in other cell types, but hepatocyte production of this interferon is little investigated. Due to the difficulty and significant costs in obtaining and culturing human primary hepatocytes, surrogate systems are widely sought. Here we used induced pluripotent stem (iPS)-derived hepatocyte-like cells (HLCs) to investigate hepatic IFNL expression in response to viral-like ligands. We demonstrate that hepatocytes rely on cytoplasmic pattern recognition receptors (PRRs) such as Protein Kinase RNA-dependent (PKR) and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLR) for the detection of double stranded RNA. Stimulation of HLCs by viral-like RNA ligands activating cytosolic RNA sensors resulted in thousand fold increase of type III interferon gene expression. These results are in contrast with type I IFN expression, which was induced to a lower extent. Concomitant induction of interferon stimulated genes, such as interferon-stimulated gene 15 (ISG15) and CXCL10, indicated the ability of HLCs to activate interferon-dependent activity. These results demonstrate that HLCs mount an innate antiviral response upon stimulation with viral-like RNA characterised by the induction of type III IFN.","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"204 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141376075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chanh Ho Quang, Trieu Huynh Trung, Tam Dong Thi Hoai, Tran Kim Hung, Huynh Ngoc Thien Vuong, Phan Tu Qui, Huyen Vu Ngo Thanh, Alexandra Moncada, Thanh Kieu Nguyen Thi, Duyen Huynh Thi Le, Ngan Nguyen-Lyle, Vuong Nguyen Lam, Lam Phung Khanh, Angela McBride, Bridget Wills, Sophie Yacoub
Glycocalyx disruption and hyperinflammatory responses are implicated in the pathogenesis of dengue-associated vascular leak, however little is known about their association with clinical outcomes of patients with dengue shock syndrome (DSS). We investigated the association of vascular and inflammatory biomarkers with clinical outcomes and their correlations with clinical markers of vascular leakage. We performed a prospective cohort study in Viet Nam. Children ≥ 5 years of age with a clinical diagnosis of DSS were enrolled into this study. Blood samples were taken daily during ICU stay and 7–10 days after hospital discharge for measurements of plasma levels of Syndecan-1, Hyaluronan, Suppression of tumorigenicity 2 (ST-2), Ferritin, N-terminal pro Brain Natriuretic Peptide (NT-proBNP), and Atrial Natriuretic Peptide (ANP). The primary outcome was recurrent shock. 90 DSS patients were enrolled. Recurrent shock occurred in 16 patients. All biomarkers, except NT-proBNP, were elevated at presentation with shock. There were no differences between compensated and decompensated DSS patients. Glycocalyx markers were positively correlated with inflammatory biomarkers, haematocrit, percentage hemoconcentration, and negatively correlated with stroke volume index. While Syndecan-1, Hyaluronan, Ferritin, and ST-2 improved with time, ANP continued to be raised at follow-up. Enrolment Syndecan-1 levels were observed to be associated with developing recurrent shock although the association did not reach the statistical significance at the P < 0.01 (OR = 1.82, 95% CI 1.07–3.35, P = 0.038). Cardiovascular and inflammatory biomarkers are elevated in DSS, correlate with clinical vascular leakage parameters and follow different kinetics over time. Syndecan-1 may have potential utility in risk stratifying DSS patients in ICU.
{"title":"Kinetics of cardiovascular and inflammatory biomarkers in paediatric dengue shock syndrome","authors":"Chanh Ho Quang, Trieu Huynh Trung, Tam Dong Thi Hoai, Tran Kim Hung, Huynh Ngoc Thien Vuong, Phan Tu Qui, Huyen Vu Ngo Thanh, Alexandra Moncada, Thanh Kieu Nguyen Thi, Duyen Huynh Thi Le, Ngan Nguyen-Lyle, Vuong Nguyen Lam, Lam Phung Khanh, Angela McBride, Bridget Wills, Sophie Yacoub","doi":"10.1093/oxfimm/iqae005","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae005","url":null,"abstract":"\u0000 \u0000 \u0000 Glycocalyx disruption and hyperinflammatory responses are implicated in the pathogenesis of dengue-associated vascular leak, however little is known about their association with clinical outcomes of patients with dengue shock syndrome (DSS). We investigated the association of vascular and inflammatory biomarkers with clinical outcomes and their correlations with clinical markers of vascular leakage.\u0000 \u0000 \u0000 \u0000 We performed a prospective cohort study in Viet Nam. Children ≥ 5 years of age with a clinical diagnosis of DSS were enrolled into this study. Blood samples were taken daily during ICU stay and 7–10 days after hospital discharge for measurements of plasma levels of Syndecan-1, Hyaluronan, Suppression of tumorigenicity 2 (ST-2), Ferritin, N-terminal pro Brain Natriuretic Peptide (NT-proBNP), and Atrial Natriuretic Peptide (ANP). The primary outcome was recurrent shock.\u0000 \u0000 \u0000 \u0000 90 DSS patients were enrolled. Recurrent shock occurred in 16 patients. All biomarkers, except NT-proBNP, were elevated at presentation with shock. There were no differences between compensated and decompensated DSS patients. Glycocalyx markers were positively correlated with inflammatory biomarkers, haematocrit, percentage hemoconcentration, and negatively correlated with stroke volume index. While Syndecan-1, Hyaluronan, Ferritin, and ST-2 improved with time, ANP continued to be raised at follow-up. Enrolment Syndecan-1 levels were observed to be associated with developing recurrent shock although the association did not reach the statistical significance at the P < 0.01 (OR = 1.82, 95% CI 1.07–3.35, P = 0.038).\u0000 \u0000 \u0000 \u0000 Cardiovascular and inflammatory biomarkers are elevated in DSS, correlate with clinical vascular leakage parameters and follow different kinetics over time. Syndecan-1 may have potential utility in risk stratifying DSS patients in ICU.\u0000","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"29 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141271590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Guerrero, Sokchea Lay, E. Piv, Chansophea Chhin, Sokkeang Leng, Ratana Meng, Kim Eng Mam, P. Pean, Amelie Vantaux, Sebastien Boyer, Dorothée Missé, T. Cantaert
Dengue virus (DENV) poses a global health threat, affecting millions annually with no specific therapy and limited vaccines. Mosquitoes, mainly Aedes aegypti and Aedes albopictus worldwide, transmit DENV through their saliva during blood meals. In this study, we aimed to understand how Aedes mosquito saliva modulate skin immune responses during DENV infection in individuals living in mosquito-endemic regions. To accomplish this, we dissociated skin cells from Cambodian volunteers and incubated them with salivary gland extract (SGE) from 3 different mosquito strains: Ae. aegypti USDA strain, Ae. aegypti and Ae. albopictus wild type (WT) in the presence/absence of DENV. We observed notable alterations in immune skin cells phenotypes subsequent to exposure to Aedes salivary gland extract (SGE). Specifically, exposure lead to an increase in the frequency of macrophages expressing chemokine receptor CCR2, and neutrophils expressing CD69. Additionally, we noted a substantial increase in the percentage of macrophages that became infected with DENV in the presence of Aedes SGE. Differences in cellular responses were observed when Aedes SGE of three distinct mosquito strains were compared. Our findings deepen the understanding of mosquito saliva's role in DENV infection and skin immune responses in individuals regularly exposed to mosquito bites. This study provides insights into skin immune cell dynamics that could guide strategies to mitigate DENV transmission and other arbovirus diseases.
{"title":"In-Vitro assessment of cutaneous immune responses to aedes mosquito salivary gland extract and dengue virus in cambodian individuals","authors":"David Guerrero, Sokchea Lay, E. Piv, Chansophea Chhin, Sokkeang Leng, Ratana Meng, Kim Eng Mam, P. Pean, Amelie Vantaux, Sebastien Boyer, Dorothée Missé, T. Cantaert","doi":"10.1093/oxfimm/iqae003","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae003","url":null,"abstract":"\u0000 Dengue virus (DENV) poses a global health threat, affecting millions annually with no specific therapy and limited vaccines. Mosquitoes, mainly Aedes aegypti and Aedes albopictus worldwide, transmit DENV through their saliva during blood meals. In this study, we aimed to understand how Aedes mosquito saliva modulate skin immune responses during DENV infection in individuals living in mosquito-endemic regions. To accomplish this, we dissociated skin cells from Cambodian volunteers and incubated them with salivary gland extract (SGE) from 3 different mosquito strains: Ae. aegypti USDA strain, Ae. aegypti and Ae. albopictus wild type (WT) in the presence/absence of DENV.\u0000 We observed notable alterations in immune skin cells phenotypes subsequent to exposure to Aedes salivary gland extract (SGE). Specifically, exposure lead to an increase in the frequency of macrophages expressing chemokine receptor CCR2, and neutrophils expressing CD69. Additionally, we noted a substantial increase in the percentage of macrophages that became infected with DENV in the presence of Aedes SGE. Differences in cellular responses were observed when Aedes SGE of three distinct mosquito strains were compared.\u0000 Our findings deepen the understanding of mosquito saliva's role in DENV infection and skin immune responses in individuals regularly exposed to mosquito bites. This study provides insights into skin immune cell dynamics that could guide strategies to mitigate DENV transmission and other arbovirus diseases.","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"468 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140759597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}