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. 2009 Jun;5(2):197-204.
doi: 10.1007/s11302-009-9130-x. Epub 2009 Feb 12.

The P2X(7) receptor and intracellular pathogens: a continuing struggle

Robson Coutinho-Silva  1 , Gladys Corrêa, Ali Abdul Sater, David M Ojcius
Affiliations

The P2X(7) receptor and intracellular pathogens: a continuing struggle

Robson Coutinho-Silva et al. Purinergic Signal. 2009 Jun.

Abstract

The purinergic receptor, P2X(7), has recently emerged as an important component of the innate immune response against microbial infections. Ligation of P2X(7) by ATP can stimulate inflammasome activation and secretion of proinflammatory cytokines, but it can also lead directly to killing of intracellular pathogens in infected macrophages and epithelial cells. Thus, while some intracellular pathogens evade host defense responses by modulating with membrane trafficking or cell signaling in the infected cells, the host cells have also developed mechanisms for inhibiting infection. This review will focus on the effects of P2X(7) on control of infection by intracellular pathogens, microbial virulence factors that interfere with P2X(7) activity, and recent evidence linking polymorphisms in human P2X(7) with susceptibility to infection.

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Figures

Fig. 1
Fig. 1
Pathogen clearance by infected cells. Ligation of P2X7 by extracellular ATP can promote elimination of intracellular pathogens (left side). P2X7 signaling can lead to PLD activation and/or ROS production, both of which can lead to killing of the pathogens. PLD has its effect primarily through stimulation of fusion between parasitophorous vacuoles and lysosomes, and subsequent killing of pathogens in acidic phagolysosomes (right side)
Fig. 2
Fig. 2
Mechanisms of pathogen evasion. Parasites have several methods to avoid antimicrobial activity of infected cells, including interference of intracellular signaling pathways (in response to ROS) and membrane trafficking (via PLD). Successful pathogens (green) can thus replicate, complete their infection cycle, and escape to the extracellular environment (right side). In addition, some protozoan parasites express ecto-ATPases (green with orange hat), which can contribute to cleavage of extracellular ATP, preventing P2X7R activation (left side). Some intracellular bacteria also protect the infected cell by secreting enzymes that consume extracellular ATP (not shown)
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