TABLE 1.

Selected attributes, processes, and functions of neutrophils discovered using genome-wide approaches.

Attribute, function or process	Discovery or conclusion	Ref.
Granulopoiesis	Positive correlation between protein and mRNA levels during neutrophil development	(Iida et al., 2005; Lian et al., 2002; Lian et al., 2001)
	Temporal regulation of transcripts encoding granule proteins during neutrophilic differentiation of human primary bone marrow progenitors	(Theilgaard-Monch et al., 2005)
	Lineage specificity in gene expression among hematopoietic cells	(Kluger et al., 2004)
	Mature neutrophils have increased capacity to respond to interferon-gamma	(Martinelli et al., 2004)
	Coordinate gene regulation during cellular differentiation is influenced by chromosomal organization	(Kosak et al., 2007)
	DNA methylation patterns differ during stages of granulopoesis and mature PMNs	(Ronnerblad et al., 2014)
	miRNAs influence key transcription factors during granulopoesis	(Larsen et al., 2013; Yuan et al., 2018)
	In mature neutrophils, G-CSF treatment as a model of emergency granulopoesis leads to reduced transcripts of four major granule proteins involved in bactericidal activity	(Pedersen et al., 2016)
	Identification of a unipotent neutrophil progenitor	(Zhu et al., 2018)
Heterogeneity	Identification of neutrophil subsets in populations of tumor-infiltrating myeloid cells; identification of neutrophil subsets in peripheral blood of healthy subjects	(Kippner et al., 2014; Zilionis et al., 2019)
Recruitment
Chemotaxis	Regulation of chemotaxis by miRNA	(Bauernfeind et al., 2012; Dorhoi et al., 2013; Johnnidis et al., 2008)
Priming	Comprehensive view of the similarities and differences between priming agents and phagocytic stimuli	(Wright et al., 2013; Zhang et al., 2004)
	Lipopolysaccharide elicits changes in expression of interferon-stimulated genes (ISGs)	(Fessler et al., 2002; Malcolm et al., 2003)
Transmigration	Regulates cell fate and promotes wound healing	(Theilgaard-Monch et al., 2004)
Spontaneous apoptosis	Comprehensive view of molecules involved in the loss of neutrophil function during apoptosis. This study reveals the remarkable number of host defense-related molecules that are down-regulated during constitutive (spontaneous) neutrophil apoptosis.	(Kobayashi, Voyich, Whitney, et al., 2005)
	PMNs undergoing apoptosis exhibit a pro resolving lipid mediator profile	(Dalli & Serhan, 2012)
Phagocytosis
Phagocytosis-induced cell death (PICD)	Phagocytosis induces a neutrophil apoptosis differentiation program, a final stage of transcriptionally regulated PMN maturation. Neutrophil programmed cell death is regulated at the level of gene expression, and thus PMN gene regulation facilitates resolution of inflammation.	(Kobayashi et al., 2002)
	Comprehensive view of the down-regulation of pro-inflammatory capacity during PICD. The study highlights the sheer magnitude of change in proinflammatory molecules during apoptosis.	(Kobayashi, Voyich, Braughton, et al., 2003)
	Bacterial pathogens modulate the neutrophil apoptosis differentiation program. This work forms the basis of a paradigm for the resolution of infection. The discovery is that there are two possible outcomes of neutrophil-bacteria interactions; one leads to resolution of infection and the other to disease (see Figure 4).	(Kobayashi, Braughton, et al., 2003)
	PICD is delayed in neutrophils from chronic granulomatous disease patients and ROS are critical for PICD.	(Kobayashi et al., 2004)
	Neutrophil phagosomes contain proteins typically associated with the endoplasmic reticulum. This finding suggests neutrophil phagosomes have potential for antigen processing	(Burlak et al., 2006)
Delayed apoptosis	A. phagocytophilum fails to induce the apoptosis differentiation program in human neutrophils.	(Borjesson et al., 2005; Lee & Goodman, 2006; Lee et al., 2008; Sukumaran et al., 2005)
	Leishmania major and A. phagocytophilum enhance release of pro-inflammatory LTB4, and concomitantly decrease production of pro-resolving LXA4	(Plagge & Laskay, 2017)
	GM-CSF enhances neutrophil pro-inflammatory capacity by up-regulating dozens of molecules involved in host defense. Neutrophils have potential for antigen presentation.	(Kobayashi, Voyich, Whitney, et al., 2005; Lin & Lore, 2017; Polak et al., 2019; Vono et al., 2017)