Purinergic Signalling (2007) 3:83–90 P2 receptor subtype involved Not determined P2X7, P2Y P2X7 P2Y(?) P2X7+P2(?) P2X7 P2X7 P2X7 P2X7 P2X7 (?) P2X7 P2X7 References [19] [20], [23] [42] [11] [21] [41] [22] [52] [51] [64] [65] [54] Table 1 Effect of extracellular ATP on intracellular pathogens Pathogen Effect described 86 Cell type Human macrophages Human macrophages Mouse macrophage Human macrophages Mouse macrophages and J774 cell line Bovine macrophages J774 macrophage Mouse thymocytes Mouse macrophages Mouse macrophages Mouse macrophages C. trachomatis BCG BCG BCG—M. tuberculosis H37Ra BCG M. tuberculosis (H37Rv, Erdman and CSU#93) BCG BCG C. caviae T. cruzi T. cruzi L. amazonensis; L. donovani –Mycobacterial clearance –Mycobacterial clearance –Acidification of mycobacteria-containing phagosomes –Inhibition of P2X7-associated permeabilsation Production of NO and ROI Mycobacterial clearance; PLD activation Mycobacterial clearance, PLD activation, phagosome– lysosome fusion Mycobacterial clearance, increase P2X7 mRNA – Chlamydial clearance– Inhibition of P2X7-mediated apoptosis Chlamydial clearance, PLD activation, phagosome– lysosome fusion Modulation of thymocyte death Inhibition of P2X7-mediated permeabilisation Increase of P2X7-mediated permeabilisation PLD=phospholipase D; ROI=reactive oxygen intermediates Conversely, as the activation of P2X7-dependent path- ways is deleterious for Chlamydia, both directly and through the demise of the macrophage, the intracellular pathogen has also evolved a mechanism for protecting its host cell. Thus, the infection of macrophages with a related species, C. psittaci (also known as C. caviae), inhibits partially ATPe-mediated macrophage death [52]. While the molecular basis for host-cell protection remains to be investigated, chlamydial infection decreases partially the ability of ATPe to induce plasma–membrane permeabilisa- tion and calcium fluxes [52]. Chlamydiae, therefore, resemble other pathogenic bacteria and protozoan parasites that attempt to protect themselves and the host cell by degrading nucleotides or hydrolysing ATP. Effects of ATPe on leishmaniasis Leishmaniasis is used to describe several diseases caused by the obligate intracellular protozoan parasite Leishmania, which infects mainly macrophages [53]. The diseases range from self-healing cutaneous lesions to visceral and poten- tially fatal disseminating infection. Leishmania infections are found in 80 countries, with a prevalence of 12 million human cases. The development of different clinical forms is associated with both the immunological status of the host and the parasite species [53]. The expression of the P2X7 receptor has recently been examined during Leishmania infection, revealing upregulation of the receptor during both in vivo and in vitro infection with L. amazonensis [54]. These changes were correlated with functional responses, as reflected by an increase in ATPe-mediated plasma– membrane permeabilisation and host-cell apoptosis ([54] and Chaves et al. (manuscript in preparation)) (Table 1). The increase in ATPe-induced membrane permeabilisation was also observed in spleen macrophages isolated from mice infected with L. donovani, suggesting that this may be a general phenomenon relevant for all Leishmania infections. It has been proposed that intracellular infection by Leishmania donovani inhibits macrophage apoptosis in- duced by growth factor deprivation [55]. In contrast, there is an increase in the ATPe-mediated apoptosis of macro- phages infected with Leishmania (our unpublished data), consistent with the increases in ATPe-mediated membrane permeabilisation. Thus, despite the production of ecto- ATPases by Leishmania [16], this strategy is not sufficient to protect the host cell against the infection-dependent upregulation in P2X7 expression. We have observed that the presence of ATPe during L. amazonensis infection does not interfere with Leishmania invasion, but the ATPe treatment of macrophages that are already infected with L. amazonensi leads to a decrease in Leishmania survival (our unpublished observations). In addition, we observed that ATPe has no effect on the