Dataset Information

Multi-omic profiling of pathogen-stimulated primary immune cells.

ABSTRACT: We performed long-read transcriptome and proteome profiling of pathogen-stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors to discover new transcript and protein isoforms expressed during immune responses to diverse pathogens. Long-read transcriptome profiling reveals novel sequences and isoform switching induced upon pathogen stimulation, including transcripts that are difficult to detect using traditional short-read sequencing. Widespread loss of intron retention occurs as a common result of all pathogen stimulations. We highlight novel transcripts of NFKB1 and CASP1 that may indicate novel immunological mechanisms. RNA expression differences did not result in differences in the amounts of secreted proteins. Clustering analysis of secreted proteins revealed a correlation between chemokine (receptor) expression on the RNA and protein levels in C. albicans- and poly(I:C)-stimulated PBMCs. Isoform aware long-read sequencing of pathogen-stimulated immune cells highlights the potential of these methods to identify novel transcripts, revealing a more complex transcriptome landscape than previously appreciated.

SUBMITTER: Salz R

PROVIDER: S-EPMC11293528 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Multi-omic profiling of pathogen-stimulated primary immune cells.

Salz Renee R Vorsteveld Emil E EE van der Made Caspar I CI Kersten Simone S Stemerdink Merel M Riepe Tabea V TV Hsieh Tsung-Han TH Mhlanga Musa M Netea Mihai G MG Volders Pieter-Jan PJ Hoischen Alexander A 't Hoen Peter A C PAC

iScience 20240706 8

We performed long-read transcriptome and proteome profiling of pathogen-stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors to discover new transcript and protein isoforms expressed during immune responses to diverse pathogens. Long-read transcriptome profiling reveals novel sequences and isoform switching induced upon pathogen stimulation, including transcripts that are difficult to detect using traditional short-read sequencing. Widespread loss of intron retention occurs ...[more]

PMID: 39091463

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Project description:BackgroundOmicron sub-variants breakthrough infections (BTIs) have led to millions of coronavirus disease 2019 (COVID-19) cases worldwide. The acute-phase immune status is critical for prognosis, however, the dynamic immune profiling of COVID-19 during the first month after BTIs remains unclear.MethodsIn this study, we monitored the immune dynamics at various timepoints in a longitudinal cohort during the first month post-BTIs through clinical evaluation, single-cell RNA sequencing (scRNA-seq), T cell receptor (TCR)/B cell receptor (BCR) sequencing, and antibody mass spectrometry.FindingsSerological analysis revealed limited impairment to functions of major organs, active cellular and humoral immunity at 2 weeks post-BTI, with significant increases in cytokines (CKs) and neutralizing antibody levels. However, 1 month post-BTI, organ function parameters and CK levels reverted to pre-infection levels, whereas neutralizing antibody levels remained high. Notably, scRNA-seq showed that lymphocytes maintained strong antiviral activity and cell depletion at 2 weeks and 1 month post-BTI, with genes CD81, ABHD17A, CXCR4, DUSP1, etc. upregulated, and genes PFDN5, DYNLRB1, CD52, etc. downregulated, indicating that lymphocytes status take longer to recover to normal levels than that routine blood tests revealed. Additionally, T cell-exhaustion associated genes, including LAG3, TIGIT, PDCD1, CTLA4, HAVCR2, and TOX, were upregulated after BTI. TCRs and BCRs exhibited higher clonotypes, mainly in CD8Tem or plasmablast cells, at 2 weeks post-BTI comparing 1 month. More IgG and IgA-type BCRs were found in the groups of 1 month post-BTI, with higher somatic hypermutation, indicating greater maturity. Verification of monoclonal antibodies corresponding to amplified BCRs highlighted the antigen-specific and broad-spectrum characteristics.InterpretationOur study elucidated the dynamic immune profiling of individuals after Omicron BA.5 sublineages BTI. Strong immune activation, antiviral response, antibody maturation and class transition at 2 weeks and 1 month after BTI may provide essential insights into pathogenicity, sequential immune status, recovery mechanisms of Omicron sublineage BTI.FundingThis study was supported by the National Key R&D Program of China, the China Postdoctoral Science Foundation, Guangdong Basic and Applied Basic Research Foundation, the National Natural Science Foundation of China, CAS Project for Young Scientists in Basic Research, and the Air Force Special Medical Center Science and Technology Booster Program.

Dataset Information

Multi-omic profiling of pathogen-stimulated primary immune cells.

Publications

Multi-omic profiling of pathogen-stimulated primary immune cells.

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