Immunological alterations mediated by adenosine during host-microbial interactions

Adenosine accumulates in inflammation and ischemia but it is more than an end-product of ATP catabolism. Signaling through different receptors with distinct, cell-specific cytoplasmic pathways, adenosine is now recognized as an inducible switch that regulates the immune system. By acting through the A(2A)AR, adenosine shapes T cell function, largely by conferring an anti-inflammatory tone on effector Th cells (Teff) and natural killer (NK)T cells. In contrast, both the A(2A)AR and A(2B)AR are expressed by antigen-presenting cells (APC) which have been shown to regulate innate responses and the transition to adaptive immunity. There is also emerging evidence that adenosine production is one mechanism that allows some pathogens as well as neoplasms to evade host defenses. This review discusses the immunoregulatory functions of adenosine and some of the interactions it may have in regulating host-microbial interactions.