Current Understanding of the Neutrophil Transcriptome in Health and Disease

Abstract

Neutrophils are key cells of the innate immune system. It is now understood that this leukocyte population is diverse in both the basal composition and functional plasticity. Underlying this plasticity is a post-translational framework for rapidly achieving early activation states, but also a transcriptional capacity that is becoming increasingly recognized by immunologists. Growing interest in the contribution of neutrophils to health and disease has resulted in more efforts to describe their transcriptional activity. Whilst initial efforts focused predominantly on understanding the existing biology, investigations with advanced methods such as single cell RNA sequencing to understand interactions of the entire immune system are revealing higher flexibility in neutrophil transcription than previously thought possible and multiple transition states. It is now apparent that neutrophils utilise many forms of RNA in the regulation of their function. This review collates current knowledge on the nuclei structure and gene expression activity of human neutrophils across homeostasis and disease, before highlighting knowledge gaps that are research priority areas.

Single-cell transcriptomics of the ventral posterolateral nucleus-enriched thalamic regions from HSV-1-infected mice reveal a novel microglia/microglia-like transcriptional response

“…Differentially expressed mRNAs were identified by significant feature comparison. A list of 6 neutrophil-related genes common to multiple diseases was used to show the neutrophil-like phenotype of “in transition” microglia/microglia-like cells [ 42 ]. UMAP dimensional reduction was used to visualize and verify clusters.…”

CXCR2 intrinsically drives the maturation and function of neutrophils in mice

“…It was essential to analyze the mechanisms underlying the differences between spleen Cxcr2-/- and WT neutrophils. RNAseq analysis of both types of isolated neutrophils confirmed the defect in maturation of spleen Cxcr2-/- neutrophils, with in particular a down regulation of genes involved in Netosis (Cathepsin D, JunB or IL-1β) ( 45 ), of Arginase-2 controlling extra-urea cycle arginine metabolism and nitric oxide synthesis, of Clec4d implicated in bacteria elimination ( 46 ) or Selplg (CD162), essential for the rolling of neutrophils ( 47 ). Several GO pathways of migration and chemotaxis constituted a down-regulated cluster, suggesting also an impairment of spleen Cxcr2-/- chemotaxis.…”

Targeting Neutrophils for Promoting the Resolution of Inflammation

“…However, the exact function of some neutrophil subpopulations remain elusive. Single cell RNA sequencing revealed transcriptomically distinct neutrophil populations, even amongst mature peripheral neutrophils ( 58 , 59 ) and neutrophils associated with chronic inflammatory states ( 58 , 60 – 62 ). Different neutrophil states in healthy mice and humans can be projected onto a signal development continuum (termed neutrotime) characterized by clearly defined poles separated by a smooth transcriptome shift ( 63 ).…”