Regulation of emergency granulopoiesis during infection

Abstract

During acute infectious and inflammatory conditions, a large number of neutrophils are in high demand as they are consumed in peripheral organs. The hematopoietic system rapidly responds to the demand by turning from steady state to emergency granulopoiesis to expedite neutrophil generation in the bone marrow (BM). How the hematopoietic system integrates pathogenic and inflammatory stress signals into the molecular cues of emergency granulopoiesis has been the subject of investigations. Recent studies in the field have highlighted emerging concepts, including the direct sensing of pathogens by BM resident or sentinel hematopoietic stem and progenitor cells (HSPCs), the crosstalk of HSPCs, endothelial cells, and stromal cells to convert signals to granulopoiesis, and the identification of novel inflammatory molecules, such as C/EBP-β, ROS, IL-27, IFN-γ, CXCL1 with direct effects on HSPCs. In this review, we will provide a detailed account of emerging concepts while reassessing well-established cellular and molecular players of emergency granulopoiesis. While providing our views on the discrepant results and theories, we will postulate an updated model of granulopoiesis in the context of health and disease.

Roles of trained immunity in the pathogenesis of periodontitis

“…43,44 Similarly, the amplified production of neutrophils from their progenitors modulated by HSPCs is called emergency granulopoiesis. 45 Important to know, HSPCs sense infectious agents either directly by expressing pattern recognition receptors (PRRs) such as toll-like receptors (TLRs), or indirectly by receptors for inflammatory cytokines and growth factors, such as IL-1β, IL-6, interferons, and GM-CSF. 17,40 Additionally, the BM niche, a specialized microenvironment consisted of multiple cellular components, including endothelial cells, mesenchymal stem/stromal cells (MSCs), osteo-lineage cells, as well as niche-forming extracellular matrix molecules, is also an important modulator of HSC proliferation and differentiation.…”

“…In response, BM HSPCs expand and enhance myeloid cell output for replenishment, a process termed emergency myelopoiesis 43,44 . Similarly, the amplified production of neutrophils from their progenitors modulated by HSPCs is called emergency granulopoiesis 45 . Important to know, HSPCs sense infectious agents either directly by expressing pattern recognition receptors (PRRs) such as toll‐like receptors (TLRs), or indirectly by receptors for inflammatory cytokines and growth factors, such as IL‐1β, IL‐6, interferons, and GM‐CSF 17,40 .…”

The metabolic basis of inherited neutropenias

“…The clearance of spent neutrophils in tissue sites is also a critical aspect of homeostasis to prevent tissue damage and effects of polypeptides, small molecules, and exosomes from spent neutrophils triggered by emergency granulopoiesis in the setting of infection. 12,13 Factors associated with oxygen tension are also of interest given the hypoxic environments where haematopoiesis proceeds robustly, first in the liver during embryogenesis and then postnatally in the bone marrow, and then subsequently in sites of tissue injury/infection. The effects of hypoxic environment may induce quiescent metabolic features in HSCs in the bone marrow with low rates of protein synthesis and selective recruitment of biochemical pathways.…”

CC16 as an Inflammatory Biomarker in Induced Sputum Reflects Chronic Obstructive Pulmonary Disease (COPD) Severity

“…18 It also has antiviral activity and can affect innate immunity. 18,19 MicroRNAs (miRNAs) are small noncoding RNAs of approximately 22 nucleotide (nt) that are involved in the negative post-transcriptional gene regulation via mRNA degradation or inhibition of their translation. [20][21][22] Recently, the dysregulation of microRNAs (miRNAs), such as microRNA-155 (miR-155) and microRNA-21 (miR-21), was found to be involved in the inflammatory response or fibrosis in pulmonary diseases.…”

“… 17 Type II IFNs (IFN-γ) is a pro-inflammatory cytokine that regulate early hematopoiesis. 18 It also has antiviral activity and can affect innate immunity. 18 , 19 MicroRNAs (miRNAs) are small noncoding RNAs of approximately 22 nucleotide (nt) that are involved in the negative post-transcriptional gene regulation via mRNA degradation or inhibition of their translation.…”