88 responses during various types of inflammatory disease. However, the involvement of P2X7 during disease is complicated by the presence of other P2 receptors, which may also contribute to either pro- or anti-inflammatory immune responses. Moreover, ATP can negatively regulate Toll-like receptor signalling, suppress LPS-induced MCP-1 and TNF-!, and augments IL-10 production in human monocytes [75]. Many infectious agents that survive in these immune effector cells may have evolved complex nucleotide-based strategies to evade the immune system. Dissection of these strategies may lead us to a better understanding of the role of nucleotide signalling in the immune response and to the development of new approaches to combat infectious diseases. Concluding remarks As large concentrations of ATP are present outside of the cell only when the cell is damaged or is part of an inflamed tissue (Fig. 1), it has been proposed that ATPe may function as a generic “danger signal,” which could alert the immune system to the presence of any type of intracellular pathogen that induces host-cell death [76–78]. Different intracellular pathogens, such as bacteria and protozoan parasites, express ecto-ATPases or other mechanisms to either inhibit or enhance ATPe-mediated death of their host cell, suggesting that ATPe may have been used by the host as an ancient danger signal, to which, intracellular pathogens have been exposed since the early evolution of the immune system. 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