Stem cells are cells that undergo self-renewal and can differentiate into multi-lineages. They are tightly regulated by their microenvironment via cell-to-cell contact and endogenous signals. With the recent discovery of Toll-like receptors (TLRs) on several types of stem cells it is possible that microbial ligands are able to influence stem cells. Indeed microbial ligands such as LPS and lipoproteins alter proliferation, differentiation, migration, and function of stem cells. In this report, I reviewed the effect of TLR activation on hematopoietic stem cells (HSCs) and multipotent stem cells (MSCs). \ud In humans most TLRs activity does not seem to affect stem cell proliferation. In mice, however, stem cell proliferation is increased after TLR activation. Stem cell differentiation can also be regulated by TLR activation. Upon exposure to microbial ligands stem cells will change their differentiation to help the initial immune response. Activation of TLRs on MSCs increases osteogenesis and decreases adipogenesis and activation on HSCs increases myeloid differentiation and the production of monocytes/macrophages and DCs. Besides altering differentiation, TLR activation alters cytokine production by stem cells and the immunosuppressive function of MSCs. In general, TLR and NOD2 activation on stem cells increases the production of pro-inflammatory cytokines. However, some studies show an increase of anti-inflammatory cytokines. The response depends on ligand dose and exposure time but other factors such as micro-environment, co-stimulatory molecules, and downstream signaling pathways also influence cytokine production. The immunosuppressive function of MSCs can be increased or inhibited by TLR activation depending on the type of signaling pathways that are activated. With the identification of innate immune receptors on stem cells and the first findings that microbial ligands can influence stem cell fate, a whole new exciting area of research has been discovered
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