Hematopoietic niches, erythropoiesis and anemia of chronic infection.

Anemia is a significant co-morbidity of chronic infections, as well as other inflammatory diseases. Anemia of chronic infection results from defective bone marrow erythropoiesis. Although the limitation of iron availability has been considered a key factor, the exact mechanisms underlying blockade in erythroid generation during infection are not fully understood. Erythropoiesis is a tightly regulated process that is very sensitive to environmental changes. During the last decade, the importance of the bone marrow hematopoietic niche has been progressively acknowledged. Several bone marrow cell types (such as macrophages, mesenchymal stem cells, and progenitor cells) and molecular mediators (such as CXCL12) have been identified as fundamental for both the maintenance of hematopoietic stem cell pluripotency and their most adequate differentiation into each hematopoietic cell lineage. Importantly, both niche-supporting cells and hematopoietic progenitors were found to be able to sense local and systemic cues to adapt the hematopoietic output to needs of the organism. Here, we review how hematopoietic progenitors and niche-supporting cells sense and respond to stress cues and suggest a potential role for the hematopoietic niche in the development of anemia of chronic infection.