Regulation of myelopoiesis by proinflammatory cytokines in infectious diseases

Abstract

Hematopoiesis is hierarchically orchestrated by a very small population of hematopoietic stem cells (HSCs) that reside in the bone-marrow niche and are tightly regulated to maintain homeostatic blood production. HSCs are predominantly quiescent, but they enter the cell cycle in response to inflammatory signals evoked by severe systemic infection or injury. Thus, hematopoietic stem and progenitor cells (HSPCs) can be activated by pathogen recognition receptors and proinflammatory cytokines to induce emergency myelopoiesis during infection. This emergency myelopoiesis counterbalances the loss of cells and generates lineage-restricted hematopoietic progenitors, eventually replenishing mature myeloid cells to control the infection. Controlled generation of such signals effectively augments host defense, but dysregulated stimulation by these signals is harmful to HSPCs. Such hematopoietic failure often results in blood disorders including chronic inflammatory diseases and hematological malignancies. Recently, we found that interleukin (IL)-27, one of the IL-6/IL-12 family cytokines, has a unique ability to directly act on HSCs and promote their expansion and differentiation into myeloid progenitors. This process resulted in enhanced production of neutrophils by emergency myelopoiesis during the blood-stage mouse malaria infection. In this review, we summarize recent advances in the regulation of myelopoiesis by proinflammatory cytokines including type I and II interferons, IL-6, IL-27, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, and IL-1 in infectious diseases.

Fluorescent poly(hydroxyurethane): Biocompatibility evaluation and selective detection ofFe(III)

“…They play important roles in cell signaling and their release has an vital effect on the behavior of cells around them . Their roles in host responses to infection, immune responses, hematopoiesis, and intercellular communication have been extensively studied . Furthermore, the assessment of cytokine release of macrophages can directly reflect the intensity and duration of inflammatory response to biomaterials .…”

Single-cell profiling of Ebola virus infectionin vivoreveals viral and host transcriptional dynamics

“…The DN monocytes were highly proliferative and their transcriptomes were more similar to bone marrow resident monocyte precursors than circulating monocytes. This suggests that they may be the product of emergency myelopoiesis, a process whereby cytokines stimulate the bone marrow to release immature myeloid lineage cells that are sometimes referred to as immunosuppressive myeloid cells (Chiba et al, 2018;Hérault et al, 2017;Sayed et al, 2019) . DNs had high expression of neutrophil granule genes such as MPO and AZU1 , suggesting that they may represent immature cells prior to the branching of neutrophil and monocyte lineages ( i.e.…”

“…The presence of proliferating DN monocytes was surprising because mature monocytes in circulation are believed to be non-dividing (van Furth et al, 1979) . However, infectious and neoplastic diseases produce cytokines such as M-CSF that induce the release of proliferating immature myeloid cells from the bone marrow, a process known as emergency myelopoiesis (Chiba et al, 2018;Cuenca et al, 2015;Sayed et al, 2019) . We therefore hypothesized that the DN population may reflect immature myeloid cells released from the bone marrow by emergency myelopoiesis.…”

Alteration of Flt3-Ligand-dependent de novo generation of conventional dendritic cells during influenza infection contributes to respiratory bacterial superinfection

“…We hypothesized that the pro-inflammatory cytokine storm following IAV infection is responsible for altering DC development in the BM. It has been reported that type I IFNs, IL-6 and TNF-α promote emergency monopoiesis in some settings [ 39 , 60 , 61 ]. Here, we found that the decrease in the number of CDPs and pre-DCs during IAV infection is independent of these cytokines.…”