P2RX7 at the Host-Pathogen Interface of Infectious Diseases

Abstract

SUMMARY The P2X7 receptor (P2RX7) is an important molecule that functions as a danger sensor, detecting extracellular nucleotides from injured cells and thus signaling an inflammatory program to nearby cells. It is expressed in immune cells and plays important roles in pathogen surveillance and cell-mediated responses to infectious organisms. There is an abundance of literature on the role of P2RX7 in inflammatory diseases and the role of these receptors in host-pathogen interactions. Here, we describe the current knowledge of the role of P2RX7 in the host response to a variety of pathogens, including viruses, bacteria, fungi, protozoa, and helminths. We describe in vitro and in vivo evidence for the critical role these receptors play in mediating and modulating immune responses. Our observations indicate a role for P2X7 signaling in sensing damage-associated molecular patterns released by nearby infected cells to facilitate immunopathology or protection. In this review, we describe how P2RX7 signaling can play critical roles in numerous cells types in response to a diverse array of pathogens in mediating pathogenesis and immunity to infectious agents.

P2X7 receptor blockade decreases inflammation, apoptosis, and enteric neuron loss during Clostridioides difficile toxin A-induced ileitis in mice

“…ATP released from dead cells can increase the activation of the P2X7 receptor and promote the secretion of proinflammatory cytokines, such as IL-1β, which in turn can induce the secretion of other cytokines[ 29 , 30 ]. In the present study, the blockade of the P2X7 receptor markedly decreased IL-1β, IL-6, KC, and TNF-α synthesis in the TcdA-challenged mouse ileum, suggesting that this receptor plays an important role in inflammation induced by C. difficile toxin.…”

The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications

“…The ATP release from immune and non-immune cells can increase as a response to pathogenic infections, while subsequent activation of P2X7R following ATP binding leads to the modulation of innate/adaptive immune responses [ 93 , 94 ]. For this reason, growing evidence indicates that P2X7R plays an important role in pathogen infection-driven inflammation [ 88 , 95 , 96 ]. The receptor has therefore been described as involved in the host response to various pathogenic infections including viruses, bacteria, fungi, protozoa, and even helminths [ 96 ].…”

“…For this reason, growing evidence indicates that P2X7R plays an important role in pathogen infection-driven inflammation [ 88 , 95 , 96 ]. The receptor has therefore been described as involved in the host response to various pathogenic infections including viruses, bacteria, fungi, protozoa, and even helminths [ 96 ].…”

Purinergic Signaling in Oral Tissues

“…This ATP interacts with P2X7R, whose expression is increased, for example, by acute infection due to Porphyromonas gingivalis , one of the pathogens most frequently associated with periodontitis, and activates the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome through a canonical pathway. Consequently, the activity of caspase-1 is promoted, which in turn induces the maturation and secretion of interleukin-1β (IL-1β) and other active ILs [ 107 , 108 , 109 ]. Additionally, ATP, again interacting with P2X7R on local fibroblasts or osteoblasts, also activates the expression of receptor activator of nuclear factor k-B ligand (RANKL), inducing the differentiation and activity of osteoclasts to modify the alveolar bone crest morphology along with cytokines such as IL-1β and tumor necrosis factors α (TNFα), known to promote osteoclastic bone resorption.…”

“…[ [107][108][109][110][111] Combined periodontal infection by P. gengivalis and F. nucleatum also activates P2X7R via ATP, additionally stimulating a non-canonical pathway coupled to the activity of caspase 11, which would also contribute to limit bacterial load.…”