Dendritic cell altered states: what role for calcium?

Ca2+-driven responses in dendritic cells (DCs) are less well characterized than in lymphocytes. When DCs undergo a sequence of activation/maturation events, typically beginning with exposure to pathogens in the periphery, Ca2+ entry into the cytosol from stores in the endoplasmic reticulum or from outside the cell can occur at various steps and participate in intracellular signaling. However, not all cellular processes identified in these cells are Ca2+ dependent. While immigration of precursor DCs into the peripheral tissues as well as emigration to secondary lymphoid sites following microbial challenge depend on processes that involve Ca2+, other processes such as DC maturation in response to Toll-like receptor agonist stimulation appear not to. Certain microbial stimuli and host-derived chemokines induce Ca2+ entry that is important for the induced responses. In this article, we review the current state of our understanding of the role of Ca2+ in DC biology and argue that homeostatic control of Ca2+ levels in these cells is critical for maintaining their proper function. We also consider evidence for intercellular transmission of Ca2+ signals between DCs that are physically linked by thin membranous extensions termed tunneling nanotubules.