Innate immune cells as homeostatic regulators of the hematopoietic niche

Abstract

Two cellular systems of paramount importance for mammalian physiology, the myeloid and the hematopoietic, have received a great deal of attention in the past decade. Myeloid leukocytes, classically involved in mediating innate immune responses, are now known to regulate other important aspects of the organism's physiology, from development to regulation of metabolic functions. In parallel, many diverse cellular and molecular components have been identified in the bone marrow (BM) that are required for the regulation and lifelong preservation of hematopoietic stem and progenitor cells (HSPC). Since the production of blood and immune elements by these multipotent cells responds to environmental signals, it is not entirely surprising that the hematopoietic niches in which HSPC are located can in turn be regulated by the immune system. We review here recent evidence demonstrating that two components of the innate immune system, macrophages and neutrophils, regulate the function of the hematopoietic niche in ways that may favor both the retention and the release of HSPC from the BM. We propose that the highly migratory nature of neutrophils, the presence of a network of tissue-resident macrophages in the BM and possibly in other tissues, and the superb capacity of these innate immune cells to respond to stress endow them with regulatory functions that are ultimately relayed to the hematopoietic niche.

It takes two to tango: Phagocyte and lymphocyte numbers in a small mammalian hibernator

“…In hibernators, that were shown to restore leukocyte numbers immediately after arousal, the major part of neutrophils (N) constituted of mature cells (Bouma et al, 2011;Inkovaara and Suomalainen, 1973; Suomalainen and Rosokivi, 1973; Szilagyi and Senturia, 1972). These findings support two established presumptions: First, the life span of immune cells is substantially prolonged during hibernation, providing that leukocytes survive the extreme physiological conditions of hibernation although the duration of the hibernation period clearly outlasts the normal life span of N and monocytes in an euthermic organism (half-life of N: $12 h, of monocytes: $60 h, in mice, comparable values in other mammals) (Basu et al, 2002;Casanova-Acebes et al, 2014;Eash et al, 2009;Lord et al, 1991;von Vietinghoff and Ley, 2008), whereas antigen-experienced (activated) L usually have longer life spans than the duration of the total hibernation period (Sprent and Tough, 1994). Second, leukocytopoiesis is virtually non-existent during torpor.…”

Distinct Sources of Hematopoietic Progenitors Emerge before HSCs and Provide Functional Blood Cells in the Mammalian Embryo

“…Although we do not yet know if neutrophils have a role in mammalian embryogenesis, fetal neutrophils exhibited antibacterial oxidation responses consistent with a role in host defense. There are also possible roles for neutrophils in angiogenesis and niche interactions as seen in the adult (Casanova-Acebes et al, 2014; Christoffersson et al, 2012). …”

Proinflammatory Proteins S100A8/S100A9 Activate NK Cells via Interaction with RAGE

“…Neutrophils constitute the majority of infiltrating cells in acute inflammatory tissues and work as phagocytes and in pathogen killing (23). In addition, numerous other functions are currently attributed to neutrophils, such as the capacity to regulate various aspects of the inflammatory, immune, angiogenic, hematopoietic, wound-healing, antiviral, and antitumoral responses (24,25). Recent evidence indicated that there is crosstalk between neutrophils and NK cells as follows: NK cellderived IFN-g modulates the survival, migration into inflammatory sites, and functional responses of neutrophils, and conversely, neutrophil-derived IL-15 and IL-18 are essential for NK cell activation and proliferation (4).…”