The role of P2 receptors in controlling infections by intracellular pathogens.
A growing number of studies have demonstrated the importance of ATP(e)-signalling via P2 receptors as an important component of the inflammatory response to infection. More recent studies have shown that ATP(e) can also have a direct effect on infection by intracellular pathogens, by modulating membrane trafficking in cells that contain vacuoles that harbour intracellular pathogens, such as mycobacteria and chlamydiae. A conserved mechanism appears to be involved in controlling infection by both of these pathogens, as a role for phospholipase D in inducing fusion between lysosomes and the vacuoles has been demonstrated. Other P2-dependent mechanisms are most likely operative in the cases of pathogens, such as Leishmania, which survive in an acidic phagolysosomal-like compartment. ATP(e) may function as a "danger signal" that alerts the immune system to the presence of intracellular pathogens that damage the host cell, while different intracellular pathogens have evolved enzymes or other mechanisms to inhibit ATP(e)-mediated signalling, which should, thus, be viewed as virulence factors for these pathogens.
Coutinho-Silva
Robson
R
Programa de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Bloco G do CCS, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, 21941-590, Brazil, rcsilva@biof.ufrj.br.
Monteiro da Cruz
Cristiane
C
Persechini
Pedro M
PM
Ojcius
David M
DM