scholarly journals Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumonia

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Alex R Schuurman ◽  
Tom DY Reijnders ◽  
Anno Saris ◽  
Ivan Ramirez Moral ◽  
Michiel Schinkel ◽  
...  
Keyword(s):  
Single Cell ◽  
Influenza A ◽  
Mononuclear Cells ◽  
Single Cell Analysis ◽  
Community Acquired Pneumonia ◽  
Type I ◽  
Cell Analysis ◽  
Peripheral Blood Mononuclear ◽  
The Common ◽  
Peripheral Immune Response

The exact immunopathophysiology of community-acquired pneumonia (CAP) caused by SARS-CoV-2 (COVID-19) remains clouded by a general lack of relevant disease controls. The scarcity of single-cell investigations in the broader population of patients with CAP renders it difficult to distinguish immune features unique to COVID-19 from the common characteristics of a dysregulated host response to pneumonia. We performed integrated single-cell transcriptomic and proteomic analyses in peripheral blood mononuclear cells from a matched cohort of eight patients with COVID-19, eight patients with CAP caused by Influenza A or other pathogens, and four non-infectious control subjects. Using this balanced, multi-omics approach, we describe shared and diverging transcriptional and phenotypic patterns—including increased levels of type I interferon-stimulated natural killer cells in COVID-19, cytotoxic CD8 T EMRA cells in both COVID-19 and influenza, and distinctive monocyte compositions between all groups—and thereby expand our understanding of the peripheral immune response in different etiologies of pneumonia.

scholarly journals Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza and other community-acquired pneumonia.

2021 ◽  
Author(s):  
Alex Schuurman ◽  
Tom Reijnders ◽  
Anno Saris ◽  
Ivan Ramirez-Moral ◽  
Michiel Schinkel ◽  
...  
Keyword(s):  
Single Cell ◽  
Host Response ◽  
Influenza A ◽  
Single Cell Analysis ◽  
Type I Interferon ◽  
Community Acquired Pneumonia ◽  
Type I ◽  
Cell Analysis ◽  
The Common ◽  
Peripheral Immune Response

Abstract The exact immunopathophysiology of community-acquired pneumonia (CAP) caused by SARS-CoV-2 (COVID-19) remains clouded by methodological heterogeneity and a lack of relevant disease controls. The absence of single-cell investigations in the broader population of patients with CAP renders it difficult to distinguish immune features unique to COVID-19 from the common characteristics of a dysregulated host response to pneumonia. We performed integrated single-cell transcriptomic and proteomic analyses in PBMCs from a matched cohort of eight patients with COVID-19, eight patients with CAP caused by Influenza A or other pathogens, and four non-infectious control subjects. Using this balanced, multi-omics approach we describe shared and diverging transcriptional and phenotypic patterns – including increased levels of type I interferon stimulated NK cells in COVID-19, cytotoxic CD8 T EMRA cells in both COVID-19 and influenza, and distinctive monocyte compositions between all groups – and thereby expand our understanding of the peripheral immune response in different etiologies of pneumonia.

scholarly journals The 2′-O-methylation status of a single guanosine controls transfer RNA–mediated Toll-like receptor 7 activation or inhibition

2012 ◽  
Vol 209 (2) ◽  
pp. 235-241 ◽  
Author(s):  
Stefanie Jöckel ◽  
Gernot Nees ◽  
Romy Sommer ◽  
Yang Zhao ◽  
Dmitry Cherkasov ◽  
...  
Keyword(s):  
Influenza A ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Thermus Thermophilus ◽  
Methylation Status ◽  
Transfer Rna ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Molecular Pattern

Foreign RNA serves as pathogen-associated molecular pattern (PAMP) and is a potent immune stimulator for innate immune receptors. However, the role of single bacterial RNA species in immune activation has not been characterized in detail. We analyzed the immunostimulatory potential of transfer RNA (tRNA) from different bacteria. Interestingly, bacterial tRNA induced type I interferon (IFN) and inflammatory cytokines in mouse dendritic cells (DCs) and human peripheral blood mononuclear cells (PBMCs). Cytokine production was TLR7 dependent because TLR7-deficient mouse DCs did not respond and TLR7 inhibitory oligonucleotides inhibited tRNA-mediated activation. However, not all bacterial tRNA induced IFN-α because tRNA from Escherichia coli Nissle 1917 and Thermus thermophilus were non-immunostimulatory. Of note, tRNA from an E. coli knockout strain for tRNA (Gm18)-2′-O-methyltransferase (trmH) regained immunostimulatory potential. Additionally, in vitro methylation of this immunostimulatory Gm18-negative tRNA with recombinant trmH from T. thermophilus abolished its IFN-α inducing potential. More importantly, Gm18-modified tRNA acted as TLR7 antagonist and blocked IFN-α induction of influenza A virus–infected PBMCs.

scholarly journals Accelerating a paradigm shift: The Common Fund Single Cell Analysis Program

2018 ◽  
Vol 4 (8) ◽  
pp. eaat8573 ◽  
Author(s):  
Ananda L. Roy ◽  
Richard Conroy ◽  
Jessica Smith ◽  
Yong Yao ◽  
Andrea C. Beckel-Mitchener ◽  
...  
Keyword(s):  
Single Cell ◽  
Paradigm Shift ◽  
Single Cell Analysis ◽  
Cell Analysis ◽  
Analysis Program ◽  
Common Fund ◽  
The Common

scholarly journals Integrated single-cell analysis revealed immune dynamics during Ad5-nCoV immunization

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qiqi Cao ◽  
Shipo Wu ◽  
Chuanle Xiao ◽  
Shuzhen Chen ◽  
Xiangyang Chi ◽  
...  
Keyword(s):  
Single Cell ◽  
Mononuclear Cells ◽  
Single Cell Analysis ◽  
Vaccine Trial ◽  
The Novel ◽  
Peripheral Blood Mononuclear ◽  
Potential Binding ◽  
Cell Type Specific ◽  
Effective Public Health ◽  
Trial Participants

AbstractCoronavirus disease 2019 (COVID-19), driven by SARS-CoV-2, is a severe infectious disease that has become a global health threat. Vaccines are among the most effective public health tools for combating COVID-19. Immune status is critical for evaluating the safety and response to the vaccine, however, the evolution of the immune response during immunization remains poorly understood. Single-cell RNA sequencing (scRNA-seq) represents a powerful tool for dissecting multicellular behavior and discovering therapeutic antibodies. Herein, by performing scRNA/V(D)J-seq on peripheral blood mononuclear cells from four COVID-19 vaccine trial participants longitudinally during immunization, we revealed enhanced cellular immunity with concerted and cell type-specific IFN responses as well as boosted humoral immunity with SARS-CoV-2-specific antibodies. Based on the CDR3 sequence and germline enrichment, we were able to identify several potential binding antibodies. We synthesized, expressed and tested 21 clones from the identified lineages. Among them, one monoclonal antibody (P3V6-1) exhibited relatively high affinity with the extracellular domain of Spike protein, which might be a promising therapeutic reagent for COVID-19. Overall, our findings provide insights for assessing vaccine through the novel scRNA/V(D)J-seq approach, which might facilitate the development of more potent, durable and safe prophylactic vaccines.

scholarly journals Fractional response analysis reveals logarithmic cytokine responses in cellular populations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Karol Nienałtowski ◽  
Rachel E. Rigby ◽  
Jarosław Walczak ◽  
Karolina E. Zakrzewska ◽  
Edyta Głów ◽  
...  
Keyword(s):  
Single Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Cell Types ◽  
Response Analysis ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Fractional Response ◽  
Different Cell Types ◽  
Cell Data

AbstractAlthough we can now measure single-cell signaling responses with multivariate, high-throughput techniques our ability to interpret such measurements is still limited. Even interpretation of dose–response based on single-cell data is not straightforward: signaling responses can differ significantly between cells, encompass multiple signaling effectors, and have dynamic character. Here, we use probabilistic modeling and information-theory to introduce fractional response analysis (FRA), which quantifies changes in fractions of cells with given response levels. FRA can be universally performed for heterogeneous, multivariate, and dynamic measurements and, as we demonstrate, quantifies otherwise hidden patterns in single-cell data. In particular, we show that fractional responses to type I interferon in human peripheral blood mononuclear cells are very similar across different cell types, despite significant differences in mean or median responses and degrees of cell-to-cell heterogeneity. Further, we demonstrate that fractional responses to cytokines scale linearly with the log of the cytokine dose, which uncovers that heterogeneous cellular populations are sensitive to fold-changes in the dose, as opposed to additive changes.

scholarly journals Fractional response analysis reveals logarithmic cytokine responses in cellular populations

2020 ◽  
Author(s):  
Karol Nienałtowski ◽  
Rachel E. Rigby ◽  
Jarosław Walczak ◽  
Karolina E. Zakrzewska ◽  
Jan Rehwinkel ◽  
...  
Keyword(s):  
Single Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Cell Types ◽  
Response Analysis ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Fractional Response ◽  
Different Cell Types ◽  
Cell Data

ABSTRACTAlthough we can now measure single-cell signaling responses with multivariate, high-throughput techniques our ability to interpret such measurements is still limited. Even interpretation of dose-response based on single-cell data is not straightforward: signaling responses can differ significantly between cells, encompass multiple signaling effectors, and have dynamic character. Here, we use probabilistic modeling and information-theory to introduce fractional response analysis (FRA), which quantifies changes in fractions of cells with given response levels. FRA can be universally performed for heterogeneous, multivariate, and dynamic measurements and, as we demonstrate, uncovers otherwise hidden patterns in single-cell data. In particular, we show that fractional responses to type I interferon in human peripheral blood mononuclear cells are very similar across different cell types, despite significant differences in mean or median responses and degrees of cell-to-cell heterogeneity. Further, we demonstrate that fractional responses to cytokines scale linearly with the log of the cytokine dose, which uncovers that cellular populations are sensitive to fold-changes in the dose, as opposed to additive changes.

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