Oxford open immunology最新文献

{"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_RM cells) are unique T-cell populations that persist in tissues for long periods awaiting re-encounter with their cognate antigen. Although T_RM cell reactivation primarily requires the presentation of cognate antigens, recent evidence has shown that, in addition to the conventional concept, T_RM cells can be reactivated without the presentation of cognate antigens. Non-cognate T_RM 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_RM 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_RM cell maintenance and reactivation and discusses the importance of effector functions that T_RM cells exert upon being presented with cognate and/or non-cognate antigens, as well as cytokines secreted by T_RM and non-T_RM 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}

{"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}

{"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}

{"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}

{"title":"Coronin 1-dependent cell density sensing and regulation of the peripheral T cell population size","authors":"Tohnyui Ndinyanka Fabrice, Mayumi Mori, Jean Pieters","doi":"10.1093/oxfimm/iqae002","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae002","url":null,"abstract":"\u0000 The establishment and maintenance of peripheral T cells is important to ensure appropriate immunity. In mammals, T cells are produced in the thymus before seeding the periphery early in life, and thereafter progressive thymus involution impairs new T cell production. Yet, peripheral T cells are maintained lifelong at approximately similar cell numbers. The question thus arises: what are the mechanisms that enable the maintenance of the appropriate number of circulating T cells, ensuring that T cell numbers are neither too low nor too high? Here, we highlight recent research suggesting a key role for coronin 1, a member of the evolutionarily conserved family of coronin proteins, in both allowing T cells to reach as well as maintain their appropriate cell population size. This cell population size controlling pathway was found to be conserved in amoeba, mice and human. We propose that coronin 1 is an integral part of a cell-intrinsic pathway that couples cell density information with prosurvival signalling thereby regulating the appropriate number of peripheral T cells.","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":" 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140217798","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}

{"title":"Post-acute sequelae of SARS-CoV-2 infection in health care workers from South Africa","authors":"Sthembile Mbotwe-Sibanda, G. Kwatra, S. Madhi, Marta C. Nunes","doi":"10.1093/oxfimm/iqae001","DOIUrl":"https://doi.org/10.1093/oxfimm/iqae001","url":null,"abstract":"\u0000 Health care workers (HCWs) are primary health providers therefore ensuring their protection and recovery from Covid-19 is of high interest. We investigated post-acute sequelae of SARS-CoV-2 infection (PASC) in HCWs who had previously been infected with SARS-CoV-2. Overall, 68 HCWs were classified as PASC according to duration in days of persisting symptoms. The 68 HCWs with PASC were split into two groups according to their mean duration of symptoms which were (8 PASC) 122 and (60 PASC) 641 days. The frequencies of common symptoms reported by HWCs with PASC were continuous headaches (45), mild cough (41), fatigue (37), myalgia (25) and shortness of breath (14). When Using the Medical Research Council (MRC) Dyspnoea Scale to examine the degree of breathlessness in relations to activity in the 68 out of the 104 HCWs with PASC we found that 4 (5.9%) reported having difficulty breathing after strenuous exercise, 19 (27.9%) were identified with shortness of breath when walking fast or when walking up a slight hill, 2 (3.0%) reported walking slower than most people on level or stopping after 15 minutes walking at own pace, 1 (1.5%) reported stopping to breath after walking 91 meters, or after a few minutes on level ground and 1 (1.5%) reported being too breathless to leave the house, or breathless when dressing/undressing. Our results highlight concern for HCWs with long-term persisting symptoms which may negatively impact their health this represents an emerging public health priority. HCWs with prolonged Covid-19 symptoms especially breathing difficulties need better diagnostic tests and treatments.","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"146 S282","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140256634","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}

{"title":"Malaria and tuberculosis co-infection-a review.","authors":"Else M Bijker, Sanjay Deshpande, Padmini Salgame, Rinn Song","doi":"10.1093/oxfimm/iqad008","DOIUrl":"https://doi.org/10.1093/oxfimm/iqad008","url":null,"abstract":"<p><p>Malaria and tuberculosis remain highly prevalent infectious diseases and continue to cause significant burden worldwide. Endemic regions largely overlap, and co-infections are expected to occur frequently. Surprisingly, malaria-tuberculosis co-infection is relatively understudied. Malaria has long been known to have immunomodulatory effects, for example resulting in reduced vaccination responses against some pathogens, and it is conceivable that this also plays a role if co-infection occurs. Data from animal studies indeed suggest clinically important effects of malaria-tuberculosis co-infection on the immune responses with potential consequences for the pathophysiology and clinical course of both infections. Specifically, rodent studies consistently show reduced control of mycobacteria during malaria infection. Although the underlying immunological mechanisms largely remain unclear, an altered balance between pro- and anti-inflammatory responses may play a role. Some observations in humans also support the hypothesis that malaria infection skews the immune responses against tuberculosis, but data are limited. Further research is needed to unravel the underlying immunological mechanisms and delineate possible implications of malaria-tuberculosis co-infection for clinical practice.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"4 1","pages":"iqad008"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813565","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}

{"title":"A targeted approach to vaccine hesitancy","authors":"Meredith Leston, Simon de Lusignan, F D Richard Hobbs","doi":"10.1093/oxfimm/iqad007","DOIUrl":"https://doi.org/10.1093/oxfimm/iqad007","url":null,"abstract":"Abstract This short communication makes the case for targeted vaccine research when attempting to counter hesitancy, especially amongst vulnerable or rarefied patient groups. Far from disincentivising vaccination, the freedom to research and publicise the limitations of these technologies for certain groups and personalising dosing, pacing, adjuvants, and time-sensitive alternatives in response is essential for optimising health outcomes while neutralising the vaccine research landscape itself. Vaccine evangelism only arouses suspicion when it is not tempered by rigorous research into differential vaccine benefit-risk in this way. That said, the long-standing politicisation of vaccination – a topic vulnerable to misinterpretation and media sensationalism – along with the commercial incentives associated with universal adoption makes more comparative and critical research difficult to fund and promote in practice. Likewise, a prescriptive approach to vaccination does little to address the issues of vaccine inequality that contribute to both hesitancy and conspiracy globally and will likely prove financially prohibitive in certain markets. These obstacles are not insurmountable, however, provided that comparative research is centrally subsidised, regulations ensure that vaccine development trials explore differentiated outcomes, especially amongst high-risk or rare groups, and findings are used to prioritise global vaccine allocation to those that stand to benefit most from them.","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"37 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136232845","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}

{"title":"The current state and future of T-cell exhaustion research.","authors":"Edward Jenkins,&nbsp;Toby Whitehead,&nbsp;Martin Fellermeyer,&nbsp;Simon J Davis,&nbsp;Sumana Sharma","doi":"10.1093/oxfimm/iqad006","DOIUrl":"10.1093/oxfimm/iqad006","url":null,"abstract":"<p><p>'Exhaustion' is a term used to describe a state of native and redirected T-cell hypo-responsiveness resulting from persistent antigen exposure during chronic viral infections or cancer. Although a well-established phenotype across mice and humans, exhaustion at the molecular level remains poorly defined and inconsistent across the literature. This is, in part, due to an overreliance on surface receptors to define these cells and explain exhaustive behaviours, an incomplete understanding of how exhaustion arises, and a lack of clarity over whether exhaustion is the same across contexts, e.g. chronic viral infections versus cancer. With the development of systems-based genetic approaches such as single-cell RNA-seq and CRISPR screens applied to <i>in vivo</i> data, we are moving closer to a consensus view of exhaustion, although understanding how it arises remains challenging given the difficulty in manipulating the <i>in vivo</i> setting. Accordingly, producing and studying exhausted T-cells <i>ex vivo</i> are burgeoning, allowing experiments to be conducted at scale up and with high throughput. Here, we first review what is currently known about T-cell exhaustion and how it's being studied. We then discuss how improvements in their method of isolation/production and examining the impact of different microenvironmental signals and cell interactions have now become an active area of research. Finally, we discuss what the future holds for the analysis of this physiological condition and, given the diversity of ways in which exhausted cells are now being generated, propose the adoption of a unified approach to clearly defining exhaustion using a set of metabolic-, epigenetic-, transcriptional-, and activation-based phenotypic markers, that we call 'M.E.T.A'.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"4 1","pages":"iqad006"},"PeriodicalIF":0.0,"publicationDate":"2023-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9956744","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}

{"title":"Endogenous antibody responses in REGN-COV2-treated SARS-CoV-2-infected individuals.","authors":"Ashwini Kurshan, Luke B Snell, Lucie Prior, Jerry C H Tam, Carl Graham, Rajeni Thangarajah, Jonathan D Edgeworth, Gaia Nebbia, Katie J Doores","doi":"10.1093/oxfimm/iqac012","DOIUrl":"10.1093/oxfimm/iqac012","url":null,"abstract":"<p><p>Neutralizing monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike glycoprotein have been developed for the treatment of COVID-19. Whilst antibody therapy has been shown to reduce the risk of COVID-19-associated hospitalization and death, there is limited understanding of the endogenous immunity to SARS-CoV-2 generated in mAb-treated patients and therefore ongoing susceptibility to future infections. Here we measure the endogenous antibody response in SARS-CoV-2-infected individuals treated with REGN-COV2 (Ronapreve). We show that in the majority of unvaccinated, delta-infected REGN-COV2-treated individuals, an endogenous antibody response is generated, but, like untreated, delta-infected individuals, there was a limited neutralization breadth. However, some vaccinated individuals who were seronegative at SARS-CoV-2 infection baseline and some unvaccinated individuals failed to produce an endogenous immune response following infection and REGN-COV2 treatment demonstrating the importance of mAb therapy in some patient populations.</p>","PeriodicalId":74384,"journal":{"name":"Oxford open immunology","volume":"4 1","pages":"iqac012"},"PeriodicalIF":0.0,"publicationDate":"2023-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280297","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}