IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections
Data files
Oct 10, 2024 version files 447.11 MB
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final_neutro.RDS
342.92 MB
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PDL1.zip
104.19 MB
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README.md
2.36 KB
Abstract
Neutrophil subsets endowed with regulatory/suppressive properties are widely regarded as deleterious immune cells that can jeopardize antitumoral response and/or antimicrobial resistance. Here, we describe a sizeable fraction of neutrophils characterized by the expression of Programmed death-ligand 1 (PD-L1) in biological fluids of humans and mice with severe viral respiratory infections (VRI). Biological and transcriptomic approaches indicated that VRI-driven PD-L1+ neutrophils are endowed with potent regulatory functions and reduced classical antimicrobial properties, as compared to their PD-L1- counterparts. VRI-induced regulatory PD-L1+ neutrophils were generated remotely in the bone marrow in an IFN-γ-dependent manner and were quickly mobilized into the inflamed lungs where they fulfilled their maturation. Neutrophil depletion and PD-L1 blockade during experimental VRI resulted in higher mortality, increased local inflammation, and reduced expression of resolving factors. These findings suggest that PD-L1+ neutrophils are important players in disease tolerance by mitigating local inflammation during severe VRI and that they may constitute relevant targets for future immune interventions.
https://doi.org/10.5061/dryad.280gb5mzw
Description of the data and file structure
We have submitted our raw single-cell datasets. The zip file contains 2 folders, one dataset for PDL1-Pos mouse neutrophils and a second dataset for PDL1-neg mouse neutrophils from IAV-infected mice.
There is a link to the R script to retrieve the list of genes for the Preneus signature and the file used ( from Evrard M, Kwok IWH, Chong SZ, Teng KWW, et al. Developmental Analysis of Bone Marrow Neutrophils Reveals Populations Specialized in Expansion, Trafficking, and Effector Functions. Immunity 2018 Feb 20;48(2):364-379.e8.)
Files and variables
File: PDL1.zip
Description: Filtered matrix/output of cellranger
PDL1
├── PDL1_neg_filtered_feature_bc_matrix
│ ├── barcodes.tsv.gz
│ ├── features.tsv.gz
│ └── matrix.mtx.gz
└── PDL1_pos_filtered_feature_bc_matrix
├── barcodes.tsv.gz
├── features.tsv.gz
└── matrix.mtx.gz
3 directories, 6 files
File: final_neutro.rds
This is a Seurat 5 Object, containing aggregated single cell data of PDL1 pos and neg. neutrophil subsets.
Please read it with R.
Script
All scripts were made using R 4.3.1.
script_Bulk_RNA_Preneus.R
This is an R script to load and retrieve the differential gene expression between granulocyte-macrophage progenitor (GMP) and pre-neutrophils (PN) using DESeq2 (Love MI, Huber W, Anders S (2014). “Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.” Genome Biology, 15, 550. doi:10.1186/s13059-014-0550-8.)
IFN-γ primes bone marrow neutrophils for regulatory functions in severe viral pneumonia.ipynb
This is a Jupyter Notebook using an R kernel to reproduce the figure of the paper. To run this script please use the rds provided named "final_neutro.rds"
There is a homemade function: basicpipe(seuratobject, dimensions_to_use, resolution_of_clustering)
This function can be found in utils.R (https://github.com/TEAM-4-CEPR/Utils/blob/main/Utils.R