Abstract
Continuous production of blood cells unfolds within a complex three-dimensional tissue scaffold established by highly organized stromal cell networks of mesenchymal, neural, and vascular origin inside bone marrow (BM) cavities. Collectively, stromal cells have been shown to serve two principal roles; first as primary participants of bone remodeling and metabolism and second as master regulators of different stages of blood cell development and production. Indeed, ample evidence demonstrates that stromal cells can sense and integrate systemic signals to shape hematopoietic responses and that these regulatory mechanisms are subverted in multiple pathologic conditions. Microbial infections are stressors that elicit potent inflammatory reactions and induce substantial alterations of hematopoietic output. Whether the cellular components of the BM stromal microenvironment are targeted by infections and participate in infection-induced hematopoiesis has not been investigated in sufficient detail to date. In this manuscript, we provide a succinct updated overview of the different cell populations that are currently known to form BM stroma. We discuss experimental evidence demonstrating that different stromal components are actively damaged or functionally altered by pathogens and/or ensuing inflammatory signals and review how these effects are known to contribute to the hematologic manifestations observed during infections.
Highlights
Bone marrow (BM) tissues are home to the continuous, lifelong, and high-throughput production of almost all blood cell lineages for the entire lifetime of adult individuals [1]
We provide a brief account of the different stromal subsets forming the bone marrow (BM) microenvironment and their regulatory control of hematopoiesis as delineated by recent studies in the murine system and summarize what is known on the pathophysiological responses of these cells to infections
Much is still to be learnt, it seems clear that BM stromal cells respond in distinct ways to different microbial infections and the inflammatory responses launched by host organisms
Summary
Bone marrow (BM) tissues are home to the continuous, lifelong, and high-throughput production of almost all blood cell lineages for the entire lifetime of adult individuals [1]. Marrow-residing, hematopoietic stem cells (HSCs) maintain high rates of mature blood cell generation by continuously differentiating along the different branches of the hematopoietic hierarchy. HSCs as well as multipotent and lineage-committed progenitor subsets self-renew, thereby preventing the rapid exhaustion of the system [2,3,4]. Sophisticated regulatory mechanisms that operate at different levels of hematopoietic development are required to promote an adequate balance between self-renewal and differentiation in order to ensure that continuous cellular production qualitatively and quantitatively matches the demands of organism [5]
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