DR52.2 DataRelease
Release Date: August 2024
New Studies: 4
Updated Studies: 1
New Studies
| SDY2735: Immunology of Severe Febrile Illness in Children | |||||||||
| Status: | New | ||||||||
| Description: | A comparative approach to severe febrile illnesses in children may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by decreased signaling by, and lower gene expression of, interferon receptors. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children. | ||||||||
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| DOI: | 10.21430/M3GTQGMQZ4 | ||||||||
| Subjects: | 152 | ||||||||
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| Publications: | None | ||||||||
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| Assays: | None | ||||||||
| Clinical Assessments: | None | ||||||||
| SDY2739: Clinical Immunity to Malaria Involves Epigenetic Reprogramming of Innate Immune Cells | |||||||
| Status: | New | ||||||
| Description: | The regulation of inflammation is a critical aspect of disease tolerance and naturally acquired clinical immunity to malaria. In our study, we demonstrate using epigenetic landscape profiling by cytometry by Time-Of-Flight (EpiTOF), that the regulation of inflammatory pathways during asymptomatic parasitemia occurs downstream of pathogen sensing, at the epigenetic level. The abundance of certain epigenetic markers (methylation of H3K27 and dimethylation of arginine residues) and decreased prevalence of histone variant H3.3 correlated with suppressed cytokine responses among monocytes of Ugandan children. Such an epigenetic signature was observed across diverse immune cell populations and not only characterized active asymptomatic parasitemia but also correlated with future long-term disease tolerance and clinical immunity when observed in uninfected children. Pseudotime analyses revealed a potential trajectory of epigenetic change that correlated with age and recent parasite exposure and paralleled the acquisition of clinical immunity. Thus, our data support a model whereby exposure to Plasmodium falciparum induces epigenetic changes that regulate excessive inflammation and contribute to naturally acquired clinical immunity to malaria. | ||||||
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| DOI: | 10.21430/M3TUYD1G2N | ||||||
| Subjects: | 12 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY2753: Bystander monocytic cells drive infection-independent NLRP3 inflammasome response to SARS-CoV-2 | |||||||||||||||
| Status: | New | ||||||||||||||
| Description: | The pathogenesis of COVID-19 is associated with a hyperinflammatory immune response. Monocytes and macrophages play a central role in this hyperinflammatory response to SARS-CoV-2. NLRP3 inflammasome activation has been observed in monocytes of patients with COVID-19, but the mechanism and consequences of inflammasome activation require further investigation. In this study, we inoculated a macrophage-like THP-1 cell line, primary differentiated human nasal epithelial cell (hNEC) cultures, and primary monocytes with SARS-CoV-2. We found that the activation of the NLRP3 inflammasome in macrophages does not rely on viral replication, receptor-mediated entry, or actin-dependent entry. SARS-CoV-2 productively infected hNEC cultures without triggering the production of inflammasome cytokines IL-18 and IL-1β. Importantly, these cytokines did not inhibit viral replication in hNEC cultures. SARS-CoV-2 inoculation of primary monocytes led to inflammasome activation and induced a macrophage phenotype in these cells. Monocytic cells from bronchoalveolar lavage (BAL) fluid, but not from peripheral blood, of patients with COVID-19, showed evidence of inflammasome activation, expressed the proinflammatory marker CD11b, and displayed oxidative burst. These findings highlight the central role of activated macrophages, as a result of direct viral sensing, in COVID-19 and support the inhibition of IL-1β and IL-18 as potential therapeutic strategies to reduce immunopathology without increasing viral replication. | ||||||||||||||
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| DOI: | 10.21430/M37BXVEH52 | ||||||||||||||
| Subjects: | 0 | ||||||||||||||
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| Publications: | None | ||||||||||||||
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| Clinical Assessments: | None | ||||||||||||||
| SDY2760: Protective effect and molecular mechanisms of human non-neutralizing cross-reactive spike antibodies elicited by SARS-CoV-2 mRNA vaccination | ||||||||||
| Status: | New | |||||||||
| Description: | The researchers investigated whether particular non-neutralizing antibodies could contribute to protection from SARS-CoV-2 infection in a lethal animal model. | |||||||||
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| DOI: | 10.21430/M3RVR85FZ3 | |||||||||
| Subjects: | 329 | |||||||||
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Updated Studies
| SDY2656: SeroNet Reference Study v2.2 | ||||||||||||||||||||||||||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||||||||||||||||||||||||||
| Description: | The National Cancer Institute’s Serological Sciences Network (SeroNet) is the nation’s largest coordinated effort to study the immune response to COVID-19 and increase the nation’s antibody testing capacity. SeroNet is a collaboration across 26 biomedical research institutions to enhance understanding of the immune response to the novel coronavirus, SARS-CoV-2. The COVID-19 Serology Laboratory coordinates much of the SeroNet research and is leading COVID-19 serology standardization efforts for the network. The SeroNet Coordinating Center, headquartered at and managed by the Vaccine, Immunity, and Cancer Directorate at the Frederick National Laboratory, provides program logistical support. SeroNet launched in October 2020, less than a year into the COVID-19 pandemic. It aims to answer critical questions regarding serology and the pandemic. SeroNet is a major component of the National Cancer Institute’s response to COVID-19. In April 2020, the National Cancer Institute received an emergency appropriation of $306 million from Congress to develop, validate, and implement serological testing and associated technologies. More than half of the funding is devoted to SeroNet. Data and studies generated by SeroNet are available on the ImmPort system, which provides a sustainable, publicly accessible archive of data generated by investigators at the National Institute of Allergy and Infectious Diseases. In early 2021, the Frederick National Laboratory supported the development and production of the Human SARS-CoV-2 Serology Standard for calibration in COVID-19 studies conducted around the U.S. and world. Lab scientists have worked with the National Cancer Institute, U.S. Food and Drug Administration, Centers for Disease Control and Prevention, other government agencies, and universities to develop sample evaluation panels to evaluate the performance (sensitivity and specificity) of antibody tests developed by external organizations before they are made available to the public. | |||||||||||||||||||||||||||||||||||||||||||||
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| DOI: | 10.21430/M3AUTZYP4Q | |||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | 909 | |||||||||||||||||||||||||||||||||||||||||||||
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| Publications: | None | |||||||||||||||||||||||||||||||||||||||||||||
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