15 research outputs found
Discrete choice experiment data for street-level urban greening in Berlin
The data presented in this DiB article are the outcome of a survey implemented in a Berlin neighborhood from January to March 2018. The data consist of socio-demographic, attitudinal and perception questions, and, most importantly, a discrete choice experiment. This dataset is complementary to the full research article, “Economic valuation of street-level urban greening: A case study from an evolving mixed-use area in Berlin” [1]. The analysis of the discrete choice experiment provided in the full article could be used to guide policy- and project-level decision-making for green building practices and urban green initiatives, while the dataset available here can be used to provide insight about how our sample population responded to the remaining parts of the questionnaire and how the experiment could be replicated in context or elsewhere in Berlin.DFG, 414044773, Open Access Publizieren 2019 - 2020 / Technische Universität Berli
Early Transcriptional Divergence Marks Virus-Specific Primary Human CD8+ T Cells in Chronic versus Acute Infection.
Distinct molecular pathways govern the differentiation of CD8+ effector T cells into memory or exhausted T cells during acute and chronic viral infection, but these are not well studied in humans. Here, we employed an integrative systems immunology approach to identify transcriptional commonalities and differences between virus-specific CD8+ T cells from patients with persistent and spontaneously resolving hepatitis C virus (HCV) infection during the acute phase. We observed dysregulation of metabolic processes during early persistent infection that was linked to changes in expression of genes related to nucleosomal regulation of transcription, T cell differentiation, and the inflammatory response and correlated with subject age, sex, and the presence of HCV-specific CD4+ T cell populations. These early changes in HCV-specific CD8+ T cell transcription preceded the overt establishment of T cell exhaustion, making this signature a prime target in the search for the regulatory origins of T cell dysfunction in chronic viral infection
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Mechanisms of Impaired Immunity in Aging and SIV-Infected Rhesus Macaques
Natural aging and human immunodeficiency virus (HIV) infection are associated with chronic low-grade systemic inflammation, immune senescence and impaired antibody (Ab) responses to vaccines such as influenza (flu). We investigated the role of Interleukin (IL)-21, a CD4 T follicular helper cells (Tfh) regulator, on flu vaccine Ab response in non-human primates (NHPs) in the context of age and controlled simian immunodeficiency virus (SIV) mac239 infection. Three doses of the flu vaccine with or without IL-21-IgFc were administered at 3-month intervals in aged SIV+ NHPs following viral suppression with anti-retroviral therapy. IL-21 treated animals demonstrated enhanced day 14 post-boost vaccine-induced Ab responses. In peripheral blood we demonstrate IL-21-induced expansion of CD4+ T central memory cells, T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressing peripheral Tfh, activated memory B cells and contraction of CD11b+ monocytes. Histocytometry analysis of draining lymph nodes (dLN) tissues from IL-21 treated animals revealed direct association between LN follicle Tfh density and frequency of circulating TIGIT+ pTfh cells. Investigation of dLN cell suspensions revealed IL-21-induced proliferation of flu-specific LN CD4 memory T cells, expansion of B cells expressing IL-21 receptor (IL-21R), and expansion of Tfh cells co-expressing TIGIT and DNAX accessory molecule (DNAM-1). Single cell RNA sequencing of dLN cells revealed IL-21-induced enhancement of B cell development and antigen presentation alongside significant inhibition of germinal center (GC) Tfh and B cell interferon signaling. We conclude that IL-21 enhances flu vaccine-induced Ab responses in aged SIV+ rhesus macaques, acting as an adjuvant modulating LN germinal center activity and potentially reversing SIV associated LN Tfh and B cell dysfunction. Strategies to supplement IL-21 in aging could be a valuable addition in the toolbox for improving vaccine responses in an aging HIV+ population.</p
Age Associated Microbiome and Microbial Metabolites Modulation and Its Association With Systemic Inflammation in a Rhesus Macaque Model
Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate the age associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 geriatric (age 19-24 years) and 4 young adult (age 3-4 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in peripheral blood mononuclear cells (PBMC) by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate, and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the gut microbiome in geriatric animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young adults. Highly abundant microbes in the geriatric animals showed a direct association with plasma biomarkers of inflammation and immune activation such as neopterin, CRP, TNF, IL-2, IL-6, IL-8 and IFN-γ. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of geriatric animals compared to the young adults. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile. Aging NHP can serve as a model for investigating the relationship of the gut microbiome to particular age-associated comorbidities and for strategies aimed at modulating the microbiome
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Age associated microbiome modulation and its association with systemic inflammation in a Rhesus Macaque Model
Abstract Background As the individual ages, the immune system decreases in activity while chronic systemic inflammation increases. The microbiome is also affected by age, decreasing in beneficial microbes while increasing in pathogenic, inflammation inducing microbes with corresponding changes in their metabolic profile. While aging is known to affect both, links between the two have been hard to uncover. Methods Four young (age 3-6 years) and 12 old (age>18 years) Rhesus macaques were recruited for the study. PBMCs and plasma were collected to investigate immune cell subsets by flow cytometry and plasma cytokines by bead based multiplex cytokine analysis respectively. Stool samples were collected by ileal loop for microbiome analysis by shotgun metagenomics and serum, gut microbial lysate and microbe-free fecal extract was used to determine metabolomics by mass-spectrometry. Results Our aging NHP model recaptured many of the features of the age-associated immune alterations, with increased inflammation and alterations in immune cells subsets with lower number of CD4 T cells and a trend of age associated alterations in maturation subsets in older animals with lower naïve and higher central memory CD4 T cells. Older animals showed a significantly different microbiome from young animals with lower abundance of Firmicutes and higher Archaeal and Proteobacterial species. Correlation analysis showed a link between microbes in older animals with systemic inflammation. Analysis of metabolites in the serum and feces showed significant differences between specific metabolites between young and older animals that can influence age-associated morbidities. Conclusion These data support the age associated alterations in microbiome profile and its association with persistent systemic inflammation and metabolome changes. Further mechanistic studies are needed to understand the relationship between inflammation and microbiome. Nevertheless, this NHP model recapitulates human age associated changes in immune, inflammatory and microbiome profiles and can be useful for designing future studies targeting microbiome modulations in aging
Application of T2*-weighted first-pass perfusion imaging in the diagnosis of breast tumors
Compromised steady‐state germinal center activity with age in nonhuman primates
Age‐related reductions in vaccine‐induced B cells in aging indicate that germinal centers (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. We found significantly lower normalized numbers of follicular PD1
hi
CD4 T (Tfh) and proliferating (Ki67
hi
) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3
hi
Lag3
hi
CD4 T cells. Furthermore, a positive correlation was found between Tfh and follicular CD8 T cells (fCD8) only in young animals. Despite the increased levels of circulating preinflammatory factors in aging, young animals had higher numbers of monocytes and granulocytes in the follicles, a profile negatively associated with numbers of Tfh cells. Multiple regression analysis showed an altered association between GC B cells and other GC immune cell populations in old animals suggesting a differential mechanistic regulation of GC activity in aging. Our data demonstrate defective baseline GC composition in old NHPs and provide an immunological base for further understanding the adaptive humoral responses with respect to aging.
Steady‐state germinal center immune reactivity is compromised in aged NHPs. This loss of reactivity is characterized by changes in many GC associated cell populations including Tfh, B cells, and follicular Tregs
A prospective evaluation of T2-weighted first-pass perfusion MR imaging in diagnosing breast neoplasms
Split dynamic MRI: Single bolus high spatial-temporal resolution and multi contrast evaluation of breast lesions
Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection
OBJECTIVE: Chronic HBV infection affects more than 250 million people worldwide and remains a global healthcare problem in part because we lack curative treatment. Sustained viral control requires HBV-specific T cells, but these become functionally impaired in chronic infection. Clinical evidence indicates that functional cure of HBV infection by the host immune response is feasible. Developing T cell-based therapies able to achieve functional cure will require identification of the requirements for a successful T cell response against HBV and the relative contribution of individual T cell specificities to HBV control. DESIGN: The phenotype and function of HBV-specific T cells were studied directly ex vivo using fluorochrome-labelled multimers. We studied multiple HBV-specific T cell specificities targeting different HBV proteins in individuals with either an acute self-limiting or chronic HBV infection. RESULTS: We detected strong T cell responses targeting multiple HBV viral proteins in acute self-limiting and low-frequency core and polymerase-specific T cells in chronic infection. Expression of the T cell inhibitory receptor PD-1, as well as T cell differentiation, T cell function and T cell regulation differed by stages and outcomes of infection. In addition, these features differed significantly between T cells targeting different HBV specificities. CONCLUSION: HBV-specific T cells with different target specificities are characterised by distinct phenotypical and functional profiles. These results have direct implications for the design of immunological studies in HBV infection, and are potentially relevant for informing immunotherapeutic approaches to induce functional cure