The immune system undergoes dynamic changes to counteract infection with pathogens or inflammation. This includes the bone marrow, whose diverse cell population is profoundly altered in proportion.
Bone marrow is a soft spongy tissue and as the name suggests, is found in the interiors of long bones. Interestingly, while the bones are integral to the musculoskeletal system, the bone marrow is the site of hematopoiesis (generation of blood cells). There are different types of blood cells, which mainly include the erythrocytes (red blood cells), lymphocytes (T cells, B cells and Natural Killer cells) and myelocytes (granulocytes and macrophages). All the different cell types arise from a common progenitor such as the hematopoietic stem cell (HSC, CD34+). The interactions found in bone marrow are critical for maintaining stem cells and regulating differentiation. Artificial bone marrow attempts to mimic many of the features found in vivo to improve cell regulation during cell culture.
HSCs must be maintained in the quiescent phase of cell cycle (G0) so that they self-renew only when needed. Specialized zones of the bone marrow, primarily the endosteal (found in the interface between medullary bone and stromal cells) and perivascular regions offer highly conducive niches for generation and maintenance of HSC populations due to its microanatomic circulatory structure and cell-cell interacting partners. Interaction between CXCR4 receptors (expressed by HSCs) and CXCL12 receptors of osteoblasts is critical for both survival and retention of HSCs in the bone marrow niche. Studies have shown that cells lose sensitivity to CXCL12 prior to moving out of the bone marrow. This has been capitalized in the transplantation technology by use of blocking agents against CXCL12 and CXCR4 to mobilize HSCs, and thereby increase harvest efficiency (Fig. 1D).
The bone marrow is thus home to the progenitor cells, the various types of blood cells and the support cells, e.g. osteoblasts and stromal cells. Recent research shows that infection with pathogens or an inflammatory response affects the viability, retention and proliferation of all these types of cells  .
Infection by pathogens can either be:
- a) direct, e.g. invasion of bone marrow residing B cells and HSCs with JC virus
- b) elsewhere in the body, which can be sensed by bone marrow cells through receptors for pattern recognition (PRRs) and cytokines (Fig. 1).
In either case, the diverse milieu of bone marrow cells show varied responses during trauma. In general, HSC and erythrocytic populations are decreased in number, while neutrophils, basophils, monocytes and macrophages are increased in number. This increase is followed by mobilization of these cells to the trauma site. B cell progenitors show a decrease in response to several infections, which in turn affects B cell development. Finer details of regulation and defining the factor/s facilitating return of the bone marrow to its normal steady-state of HSC population will prove useful in bone marrow transplant applications.
1. Zaretsky AG, Engiles JB, Hunter CA. Infection-Induced Changes in Hematopoiesis. J. Immunol (2014) 192, 27-33. d.o.i 10.4049/jimmunol.1302061