Macrophages form erythropoietic niches and regulate iron homeostasis to adapt erythropoiesis in response to infections and inflammation

• Published in: Experimental hematology 2021-11, Vol.103, p.1-14
• Main Authors: Lévesque, Jean-Pierre, Summers, Kim M., Bisht, Kavita, Millard, Susan M., Winkler, Ingrid G., Pettit, Allison R.
• Format: Article
• Language: English
• Subjects: Anemia - immunology; Animals; Erythroblasts - immunology; Erythropoiesis; Humans; Inflammation - immunology; Iron - immunology; Macrophages - immunology; Persistent Infection - immunology; Stem Cell Niche
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2021.08.011

•Macrophages in erythroblastic islands and spleen red pulp are key players of erythropoiesis and iron homeostasis.•Erythroblastic island macrophages support the maturation of erythroblasts into reticulocytes.•Erythroblastic island macrophages regulate the erythropoiesis response to infections and inflammation.•Red pulp macrophages are essential for iron recycling to feed erythropoiesis.•Macrophage activation by inflammatory cytokines and PAMPs plays important roles in anemia of inflammation. It has recently emerged that tissue-resident macrophages are key regulators of several stem cell niches orchestrating tissue formation during development, as well as postnatally, when they also organize the repair and regeneration of many tissues including the hemopoietic tissue. The fact that macrophages are also master regulators and effectors of innate immunity and inflammation allows them to coordinate hematopoietic response to infections, injuries, and inflammation. After recently reviewing the roles of phagocytes and macrophages in regulating normal and pathologic hematopoietic stem cell niches, we now focus on the key roles of macrophages in regulating erythropoiesis and iron homeostasis. We review herein the recent advances in understanding how macrophages at the center of erythroblastic islands form an erythropoietic niche that controls the terminal differentiation and maturation of erythroblasts into reticulocytes; how red pulp macrophages in the spleen control iron recycling and homeostasis; how these macrophages coordinate emergency erythropoiesis in response to blood loss, infections, and inflammation; and how persistent infections or inflammation can lead to anemia of inflammation via macrophages. Finally, we discuss the technical challenges associated with the molecular characterization of erythroid island macrophages and red pulp macrophages.